Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.74552602
However , the normal inverse relationship between free IGF 1 and IGFBP 1 was absent , and free IGF 1 changed in parallel with total IGF 1 and thus ALS and IGFBP 3 . 0.74552602^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Circulating insulin like growth factor ( IGF ) binding protein 3 ( IGFBP 3 ) , when occupied by IGF 1 or IGF 2 , combines with an acid labile glycoprotein subunit ( ALS ) to form a high molecular weight complex . ^^^ Purification involved ion exchange chromatography , and affinity chromatography on an IGF 1 IGFBP 3 column , yielding almost 1 mg ALS from 100 ml serum . ^^^ Rat ALS was almost as potent as human ALS in binding to human IGF 1 IGFBP 3 complex ( association constant , 2 . 3 nM 1 ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Thus , GH infusion was able to induce formation of the 150 kDa ternary complex by increasing circulating levels of IGF 1 , IGFBP 3 , and presumably ALS . ^^^ Administration of IGF 1 also increased serum IGF 1 and IGFBP 3 levels , although the increase in IGFBP 3 was only in the 60 kDa region of the chromatograph , suggesting that IGF 1 can induce neither ALS nor formation of the 150 kDa complex . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Insulin like growth factor binding protein 3 ( IGFBP 3 ) , after first associating with IGF 1 or IGF 2 , is able to associate with the acid labile subunit ( ALS ) and form a 140 kDa complex . ^^^ We conclude that ALS circulates in excess even in GH deficiency , is retained in the circulation for hours , and determines the stability of the 140 kDa complex , whereas IGF 1 is a limiting factor in ternary complex formation by hIGFBP 3 . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We have presently studied ternary complex formation between IGF , IGFBP 3 , and acid labile subunit ( ALS ) to further assess if IGF 1 bioavailability is increased in human fetal serum . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Fasting for 24 or 48 h decreased serum IGF 1 and ALS levels , but not hepatic ALS mRNA . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Expression of the cDNA clones in mammalian tissue culture cells results in the secretion into the culture medium of ALS activity that can form the expected complex with IGF 1 and IGF binding protein 3 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
ALS activity was quantitated by the conversion of covalent BP 53 [ 125I ] IGF 1 tracer from about 60K to about 150K . ^^^ In an assay involving competition between test substances and BP 53 IGF 1 tracer in the reaction with partially purified ALS , serum samples , acidified to inactivate endogenous ALS , reacted with potencies proportional to their immunoreactive BP 53 content . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
To further investigate the effects of IGF 1 administration upon the IGF IGFBP axis in GHRD , we have examined : 1 ) the molecular distribution of IGF 1 and IGF 2 among the IGFBPs ; 2 ) the composition and distribution of the IGFBPs , in particular IGFBP 3 ; and 3 ) the acid labile subunit ( ALS ) . ^^^ Administration of IGF 1 to GHRD patients was unable to increase concentrations of the molecular forms of IGFBP 3 , correct the aberrant distribution of IGFs among the IGFBPs , or increase serum concentrations of ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Insulin like growth factors 1 and 2 ( IGF 1 and 2 ) are present in serum primarily within a ternary complex consisting of IGF , IGF binding protein 3 ( IGF 3 ) and acid labile subunit ( ALS ) . ^^^ Immunoblot studies of human serum shows that intact ALS is decreased in growth hormone ( GH ) deficiency , increases with GH treatment , is elevated in GH excess and is unchanged with IGF 1 treatment . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We conclude that the 150 kDa fraction of adult rat serum includes 1 ) ternary complexes of intact IGFBP 3 ( which binds IGF 1 and IGF 2 with similar affinity ) , endogenous IGF 1 , and the ALS ; and 2 ) binary complexes of proteolytically nicked IGFBP 3 and ALS that bind IGF 2 preferentially . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGFBP 3 , the major circulating IGFBP , is unique in combining with a glycoprotein , the acid labile subunit ( ALS ) , to form a ternary complex with IGF 1 or IGF 2 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In these experimental conditions , the ALS is not only able to increase the mol wt of the complex , but also to greatly increase the amount of IGF 1 bound ; in the absence of ALS , radioactivity in the mol wt volume of the complexed forms was lower than that in the mol wt volume of the free form ( percentage of total [ 125I ] IGF 1 : rIGFBP 3 alone , 15 % and 44 % ; in the presence of ALS , 41 % and 24 % , respectively ) . ^^^ In both charcoal and polyethylene glycol ligand binding assays , competitive binding curves for the displacement of [ 125I ] IGF 1 from rIGFBP 3 by increasing concentrations of unlabeled IGF 1 showed an increased binding activity of rIGFBP 3 in the presence of ALS . ^^^ These data show that the non IGF binding ALS subunit of the 150 kilodalton complex can play an important role in the regulation of IGF 1 or IGF 2 binding to rIGFBP 3 and , therefore , on the levels of free IGF peptide , possibly by inducing conformational changes in rIGFBP 3 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Both prednisolone and GH alleviated the hypoglycemia , concomitantly with increases in IGF 1 , IGFBP 3 , and ALS levels . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Insulin like growth factors ( IGFs ) are found in human circulation predominantly as part of a growth hormone ( GH ) dependent complex of 125 150 kD , which is composed of three subunits : IGF 1 or IGF 2 , an acid stable IGF binding protein ( IGFBP ) 3 , and an acid labile subunit ( ALS ) . ^^^ To test the hypothesis that human bone cells ( HBCs ) , which produce abundant amounts of IGF 2 and IGFBP 3 , also produce ALS , we measured the IGF 1 , IGF 2 , IGFBP 3 , and ALS levels using specific radioimmunoassays ( RIAs ) in the conditioned medium ( CM ) of untransformed normal HBCs and SaOS 2 osteosarcoma cells treated with various effectors ( IGF 2 , osteogenic protein 1 [ OP 1 , bone morphogenetic protein 7 ] and human GH ) for 48 h . ^^^ In the IGF 2 ( 3 , 30 ng / ml ) treated HBC CM , the IGFBP 3 level was increased in a dose dependent manner but neither IGF 1 nor ALS could be detected . ^^^ In the SaOS 2 cell culture , OP 1 ( 1 , 100 ng / ml ) increased both IGF 2 and IGFBP 3 secretion but neither ALS nor IGF 1 secretion . ^^^ Treatment of HBCs with GH ( 1 , 10 , 100 ng / ml ) had no significant effect on the secretion of either IGF 1 , IGF 2 , IGFBP 3 , or ALS . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Because of its multi faceted potential as a neurotrophic factor , insulin like growth factor 1 ( IGF 1 ) has been given to hundreds of ALS patients world wide . ^^^ We found that about 25 % of ALS patients in a controlled trial of human growth hormone ( hGH ) had lower or higher than normal IGF 1 serum levels . ^^^ Many ALS patients do have some of the characteristics of type 2 diabetes mellitus , where IGF 1 therapy is also under way . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The regional distribution of nerve growth factor ( NGF ) and insulin like growth factor 1 ( IGF 1 ) receptors in human spinal cords from controls and amyotrophic lateral sclerosis ( ALS ) patients was studied by quantitative autoradiography . ^^^ In the ALS cases , although a general upregulation of IGF 1 receptors was observed throughout the spinal cord , significant increases were observed in the cervical and sacral segments compared to controls . ^^^ The cartography of IGF 1 receptors in the normal spinal cord as well as the change of these receptors in diseased spinal cord may be of importance in future treatment strategies of ALS . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The regional distribution of insulin like growth factor 1 ( IGF 1 ) receptors in human spinal cords from controls and amyotrophic lateral sclerosis ( ALS ) patients was studied by immunohistochemistry and quantitative autoradiography . ^^^ In the ALS cases although a general upregulation of IGF 1 receptors was observed throughout the spinal cord , significant increases were observed in the cervical and sacral segments compared to controls . ^^^ IGF 1 receptor immunoreactivity showed a similar pattern to that for 125I IGF 1 binding , with immunoreactivity being found in the gray matter of the spinal cord and enhanced immunoreactivity occuring in ALS patients compared to controls . ^^^ The cartography of IGF 1 receptors in the normal spinal cord as well as the change of these receptors in diseased spinal cord may be of importance in future treatment strategies of ALS . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
MEASUREMENTS : Serum insulin , GH , cortisol and IGF 1 were measured by radioimmunoassay , and serum ALS levels were assessed by Western immunoblot before and after treatment periods . ^^^ These decreases in serum ALS were smaller than the decrease in serum IGF 1 concentrations in both conditions , suggesting that IGF 1 is the limiting factor for the ternary complex formation in the catabolic states . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
GH therapy resulted in a normalization of the levels of blood sugars , IGFBP 3 , ALS , IGFBP 2 , and IGF 1 , as well as the IGF / IGFBP 3 ratio . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In the circulation , most of the IGFs are bound to a high molecular weight binding protein complex of 150 kDa that consists of IGF 1 ( or IGF 2 ) , IGFBP 3 and the acid labile subunit ( ALS ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
This variant showed reduced IGF 1 binding , and bound ALS with decreased affinity as determined by Scatchard analysis . ^^^ Specifically , the basic region [ 228 232 ] is essential for cell binding , and also affects IGF 1 binding , and independently , ALS affinity . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Antibodies against rhGH were present at day 28 , with titer being negatively related to weight gain , IGF 1 , and ALS levels . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum levels of insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , and the acid labile subunit ( ALS ) were measured in 46 GHD men participating in a 1 yr , double blind , and placebo controlled dose response study . ^^^ Significant increases in IGF 1 , IGFBP 3 , and ALS levels were observed with a dose as low as 0 . 33 IU / M ( 2 ) day . ^^^ The minimal GH dose required for normalization of the serum IGF 1 concentration was 0 . 66 IU / M ( 2 ) day , and it was 1 . 0 IU / M ( 2 ) day for ALS and IGFBP 3 . ^^^ In patients receiving 2 . 0 IU / M ( 2 ) day , the mean serum IGF 1 concentration rose to an abnormally high level , whereas at this dose , the mean IGFBP 3 and ALS levels were not different from normal . ^^^ The number of patients who developed IGFBP 3 or ALS levels that exceeded the upper normal limit was substantially smaller than the number of patients with elevated IGF 1 concentrations ( 2 , 8 , and 19 of 46 patients , respectively ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Insulin , IGF 1 , and GH increased ALS expression . ^^^ It can be concluded that biosynthesis of individual IGFBPs and of ALS are compartmentalized in adult rat liver and are distinctly regulated by insulin , IGF 1 , and GH . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF binding protein 3 ( IGFBP 3 ) , the major serum carrier of IGF 1 and IGF 2 in adults , circulates predominantly in a ternary complex with IGF and the acid labile subunit ( ALS ) . ^^^ Under ' physiological ' conditions , the affinities of ALS binding to IGF 1 IGFBP 3 and IGF 2 IGFBP 3 complexes ( 2 . 5 10 10 ( 8 ) l / mol and 5 . 8 10 10 ( 7 ) l / mol , respectively ) are 300 fold and 2000 fold lower than the constants for the formation of the corresponding binary complexes . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Circulating IGF 1 exists primarily as part of a ternary 150 kDa complex comprising equimolar amounts of IGF 1 , IGFBP 3 and acid labile subunit ( ALS ) . ^^^ It is also known that in contrast to IGF 1 and IGFBP 3 there exists a substantial quantity of unbound ALS in the circulation . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In mammals IGF 1 is part of a 150 kDa binding protein complex , which also contains a glycosylated acid labile protein ( ALS ) and a glycosylated acid stable IGF binding subunit IGFBP 3 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In contrast , the ternary complex and its components , IGF 1 , IGFBP 3 and ALS increased with gestation . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In addition , radioimmuno assays for insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , acid labile subunit ( ALS ) and IGFBP 1 were performed . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
As demonstrated by gel permeation chromatography , the acid labile subunit ( ALS ) purified from human serum , incubated for 2 h at 20 degrees C with [ 125I ] IGF 1 and rIGFBP 3 , is able to increase not only the molecular weight ( mol . wt . ) of the IGF IGFBP 3 complex , but also the amount of IGF 1 bound . ^^^ In both charcoal and polyethylene glycol ligand binding assays , competitive binding curves for the displacement of [ 125I ] IGF 1 from rIGFBP 3 by increasing concentrations of unlabeled IGF 1 showed an increased binding activity of rIGFBP 3 in the presence of ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Adult rat serum contains two types of 150 kDa IGFBP complexes : ternary complexes containing bound IGF 1 , intact IGFBP 3 and the acid labile subunit ( ALS ) , and binary complexes that contain ALS and proteolytically nicked IGFBP 3 but which lack bound IGF . ^^^ We present evidence that the binary complexes containing proteolytically nicked IGFBP 3 can be formed in two ways : by direct association of IGFBP 3 with ALS in the absence of IGF , and by proteolysis of IGFBP 3 within 150 kDa ternary complexes , resulting in increased dissociation of IGF 1 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Distribution and levels of insulin like growth factor ( IGF 1 and IGF 2 ) and insulin receptor binding sites in the spinal cords of amyotrophic lateral sclerosis ( ALS ) patients . ^^^ In this study , we compared the anatomical distribution of [ 125I ] IGF 1 , [ 125I ] IGF 2 and [ 125I ] insulin binding sites in thoracic spinal cords from patients who died of amyotrophic lateral sclerosis ( ALS ) and normal controls . ^^^ Highly significant ( P < 0 . 001 ) increases in the density of [ 125I ] IGF 1 and [ 125I ] IGF 2 binding were apparent in various laminae of the cord of ALS patients with increased binding being particularly evident in the ventral horn and the intermediate zone . ^^^ Taken together , these data reveal significant increases in both [ 125I ] IGF 1 and [ 125I ] IGF 2 binding levels in the spinal cords of ALS patients albeit to different extents . ^^^ These findings may be of relevance for future therapeutic strategies aimed at slowing the progression of this chronic neurodegenerative disease , as recently suggested by the beneficial therapeutic effects of an IGF 1 treatment in ALS patients . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum levels of insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , the acid labile subunit ( ALS ) , insulin , and IGFBP 1 were evaluated as indicators of body composition during GH replacement therapy in 20 GH deficient patients ( 9 women and 11 men ) , aged 22 57 yr , with IGF 1 levels below 2 SD . ^^^ Serum levels of IGF 1 , ALS , and IGFBP 3 above the normal range were reached in seven , five , and three subjects , respectively , after 12 months of GH therapy . ^^^ IGF 1 and ALS levels , but not IGFBP 3 levels , correlated with the total daily GH dose ( r = 0 . 676 ; P = 0 . 001 and r = 0 . 631 ; P = 0 . 003 ) . ^^^ At 12 months , the LBM values were significantly correlated to the IGF 1 levels ( r = 0 . 718 ; P < 0 . 001 ) , but not to ALS or IGFBP 3 levels . ^^^ In conclusion , both IGF 1 and ALS can be used as indicators to avoid GH excess during replacement therapy , but only IGF 1 relates to changes in LBM . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Because their previous in vitro studies indicated that hIGFBP 3 only bound to ALS in the presence of IGF 1 , and because little free IGF 1 is present in plasma , the authors postulated that IGF 1 had been mobilized to the circulation to saturate the 150 kDa hIGFBP 3 complexes . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Most of the IGF 1 in plasma circulates in a 150 kDa complex that contains IGF binding protein 3 ( IGFBP 3 ) and an acid labile subunit ( ALS ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
After 12 months of study , the 30 children receiving rhGH showed : ( 1 ) greater increase in height ( 9 . 1 + / 2 . 8 vs . 5 . 5 + / 1 . 9 cm , P < 0 . 0001 ) ; ( 2 ) increases in serum levels of IGF 1 , IGF 2 , free IGF 1 , IGFBP 3 and acid labile subunit ( ALS ) ; ( 3 ) a greater decrease in serum IGFBP 1 levels ; and ( 4 ) no significant difference in serum IGFBP 2 levels , when compared to the 14 control patients . ^^^ The change in height SDS after 12 months of rhGH ( +0 . 8 ) in the 30 treated children correlated significantly and positively with serum ALS , IGFBP 3 , total IGF , IGF 1 , IGF 2 and free IGF 1 levels measured during treatment . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Most recently , a clinical trial has revealed the beneficial effects of IGF 1 in amyotrophic lateral sclerosis ( ALS ) , a degenerative disease of the motoneurones . ^^^ We review briefly here experimental and clinical information that suggests the potential usefulness of IGF 1 in the treatment of certain neurodegenerative diseases , including ALS , Alzheimer ' s disease , various neuropathies and brain trauma . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The circulating insulin like growth factors ( IGF 1 and 2 ) occur largely as components of a 140 kDa protein complex with IGF binding protein 3 and the acid labile subunit ( ALS ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Both treatments increase serum ALS , IGFBP 3 , and IGF 1 levels , and decrease IGFBP 2 , whereas IGFBP 6 is unaffected . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We have studied the effects of the somatostatin analog octreotide , IGF 2 des ( 1 3 ) IGF 1 , transforming growth factor ( TGF ) beta 1 and tri iodothyronine ( T 3 ) on ALS secretion into the medium conditioned by rat hepatocytes in primary culture . ^^^ RESULTS : The results demonstrate that : 1 ) octreotide in vitro produces a dose dependent inhibition of both basal and GH stimulated ALS secretion into the hepatocyte conditioned medium ; 2 ) the release of ALS by adult rat hepatocytes is not affected by the presence during the incubation of des ( 1 3 ) IGF 1 or IGF 2 ; 3 ) an inhibitory effect , although only with very high doses , can be observed after treatment with TGF beta 1 ; and 4 ) a small but significant increase of ALS released into the medium can be seen when hepatocytes are treated with T 3 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum ALS fractionated by gel filtration high performance liquid chromatography eluted in a single peak at approximately 150 kDa with IGF 1 and IGFBP 3 , but appeared at about 400 500 kDa after sample acidification and fractionation under acidic condition . ^^^ ALS in adult sera more tightly correlated with IGFBP 3 than IGF 1 or IGF 2 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We have evaluated the effect of long term IGF 1 treatment on serum IGF binding protein ( IGFBP ) 3 and the acid labile subunit ( ALS ) in three sibling with Laron syndrome caused by a GH post receptor defect and with normal GHBP . ^^^ We conclude that IGF 1 treatment induces and initial suppression and then an increase in the IGFBP 3 and ALS concentrations , confirming data from animal experiments that IGFBP 3 synthesis is not solely under GH control . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Reduced pulsatile fraction of TSH , GH , and PRL secretion and low serum concentrations of T 4 , T 3 , insulin growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , and the acid labile subunit ( ALS ) were documented in the untreated state . ^^^ Pulsatile GH secretion was amplified > 6 and > 10 fold , respectively , by GHRP 2 and GHRH + GHRP 2 infusions , generating mean increases of serum IGF 1 ( 66 % and 106 % ) , IGFBP 3 ( 50 % and 56 % ) , and ALS ( 65 % and 97 % ) within 45 h . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Analysis of the distribution of IGF 1 , IGF 2 and IGFBP 3 in fluid from healthy and atretic follicles revealed that the majority of these growth factors ( > 80 % of total IGF 2 ) were in the 150KDa complex , indicating that the ALS present was functional , in that it formed the ternary complex with a molecule of IGFBP 3 and IGF . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Immunoblot studies of the acid labile subunit ( ALS ) in biological fluids , normal human serum and in children with GH deficiency and GH receptor deficiency before and after long term therapy with GH or IGF 1 respectively . ^^^ OBJECTIVE : The aims of this investigation were ( a ) to study the presence of immunoreactive forms of the acid labile subunit ( ALS ) in different human biological fluids , ( b ) to define the age dependence of serum ALS in normal children and adults and ( c ) to compare the regulation of ALS by GH or IGF 1 in children with GH deficiency ( GHD ) and GH receptor deficiency ( GHRD ) before and after 1 year of therapy with GH or IGF 1 , respectively . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
MEASUREMENTS : Circulating levels of total IGF 1 , free and bound IGF 1 , Insulin , IGFBP 1 , IGFBP 3 , ALS , catecholamines and potassium were measured . ^^^ There was no significant change in IGFBP 3 or ALS during the IGF 1 or insulin infusions . ^^^ IGF 1 and insulin under conditions of adequate substrate supply have acute effects on IGFBP 1 and potassium physiology , but have little effect on IGFBP 3 , ALS or catecholamines . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Significant increases were found in three of four of the main circulating IGF binding proteins in ALS patients , whereas serum IGF 1 and insulin levels were significantly reduced . ^^^ These results suggest an involvement of the peripheral IGF 1 trophic system in ALS . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We have therefore studied the effects of a single subcutaneous dose of rhIGF 1 ( 40 micrograms / kg at 1800 h ) , when compared with an untreated control night , in 17 subjects with IDDM , on serum concentrations of IGF 1 , IGF 2 , IGFBP 3 , acid labile subunit ( ALS ) , and IGFBP 3 proteolysis . ^^^ On the baseline night , IGFBP 3 levels correlated with the sum of IGF 1 and IGF 2 ( r = 0 . 73 , P = 0 . 02 ) and with levels of the ALS ( r = 0 . 7 , P = 0 . 002 ) . ^^^ However after rhIGF 1 , the sum of IGF 1 and IGF 2 no longer correlated with IGFBP 3 , whereas the relationship with ALS was maintained . ^^^ This can not be explained by alterations in IGFBP 3 proteolysis , and may relate to the relative stability of ALS / IGFBP 3 when complexed principally with IGF 1 rather than IGF II . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
GH treatment significantly increased serum levels of total IGF 1 from 98 ( 68 ) to 323 ( 126 ) microg / l , free IGF 1 from 0 . 48 ( 0 . 47 ) to 2 . 24 ( 1 . 66 ) microg / l , IGFBP 3 from 1 , 874 ( 1 , 178 ) to 3 , 520 ( 778 ) microg / l and ALS levels from 9 , 182 ( 5 , 524 ) to 16 , 872 ( 6 , 278 ) microg / l ( all p < 0 . 0001 ) . ^^^ In conclusion , GH replacement therapy in 13 GH deficient young adult males resulted in significant increases in total and free IGF 1 as well as in ALS levels in all patients , but had no significant effect on : ( 1 ) the pituitary FSH and LH response to GnRH ; ( 2 ) basal and hCG stimulated levels of androgens and SHBG ; ( 3 ) basal inhibin B levels ; ( 4 ) ACTH stimulated cortisol secretion . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The second aim of this project was to assess the changes in distribution of the immunoreactive forms of IGFBP 3 and IGF 1 among the ternary ( ALS / IGFBP 3 / IGF ) complex , the binary ( IGFBP 3 / IGF ) complex , and uncomplexed IGF during the first year of GH therapy , and to explore further the correlation with growth response to GH . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We have recently described a competitive binding assay for rat insulin like growth factor binding protein 3 ( IGFBP 3 ) based on the ability of IGFBP 3 to form a ternary complex with the acid labile subunit ( ALS ) in the presence of IGF 1 . ^^^ Nonfasting serum levels of IGFBP 3 were compared with those of total ( extractable ) IGF 1 ( tIGF 1 ) and ALS as well as IGFBP 3 determined by ligand blotting . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In addition to a direct stimulation of IGF 1 and ALS expression , GH inhibits IGFBP 1 serum levels and IGFBP 2 expression in an indirect manner , possibly facilitating enhanced IGF bioavailability to target tissues . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Over 75 % of the circulating insulin like growth factors ( IGF 1 and 2 ) are bound in 140 kDa ternary complexes with IGF binding protein 3 ( IGFBP 3 ) and the 84 86 kDa acid labile subunit ( ALS ) , a glycoprotein containing 20 kDa of carbohydrate . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Ternary complex formation by the glycovariants in the presence of ALS and excess IGF 1 was not significantly different from that of fully glycosylated recombinant human ( rh ) IGFBP 3 [ Ka ( fully glycosylated ) =12 . 5+ / 4 . 1 l / nmol ; mean Ka ( all mutants ) =22 . 1+ / 3 . 0 l / nmol ] . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Chronic liver disease was characterised by low serum IGF 1 , IGF 2 , IGFBP 3 and ALS levels with raised IGFBP 1 and 2 levels . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We have recently shown that insulin like growth factor ( IGF ) binding protein 5 forms ternary complexes with IGF 1 or IGF 2 and the acid labile subunit ( ALS ) ( Twigg , S . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Circulating levels of IGF 1 , IGFBP 3 and ALS , and their degree of association in the ternary complex in the fetus increased with gestational age . ^^^ In serum from deliveries > 35 weeks both ALS and IGFs were limiting but approximately 25 % of IGFBP 3 was unable to form the ternary complex even in the presence of excess ALS and IGF 1 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Measurements of ALS and IGFBP 3 added no useful extra information to IGF 1 in managing the dose titration . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Circulating insulin like growth factor 1 ( IGF 1 ) is predominantly bound in the trimeric complex comprised of IGF binding protein 3 ( IGFBP 3 ) and acid labile subunit ( ALS ) . ^^^ Circulating concentrations of IGF 1 , IGFBP 3 and ALS are believed to reflect the GH secretory status , but the clinical use of ALS determination is not known . ^^^ We found : 1 ) no significant arteriovenous gradient over the liver ofALS , IGF 1 , and IGFBP 3 ; 2 ) the diurnal variation of ALS was 12 % ( mean coefficient of variation percent ) ; 3 ) ALS levels increased throughout childhood with maximal levels in puberty , with a subsequent decrease with age in adults ; and 4 ) ALS levels were below 2 SD in 57 of 79 GHD patients ( sensitivity 72 % ) and above 2 SD in 22 of 29 patients with normal GH response ( specificity 76 % ) , which was similar , compared with the diagnostic utility of IGF 1 and IGFBP 3 . ^^^ Finally , our findings indicate that hepatic ALS production is not measurable by this approach or , alternatively , that the liver is not the primary source of circulating ALS , IGF 1 , or IGFBP 3 in humans . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The present study suggested that ALS was regulated by nutritional status , the same as IGF 1 , IGFBP 2 and IGFBP 3 ; but the serum IGFBP 2 was the best predictor of BMI as nutritional status marker among the parameters in patients with anorexia nervosa . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
With the use of a rat model , this study examined the interaction between AA input ( 1 . 27 and 0 . 62 g N . kg body wt ( 1 ) . 24 h ( 1 ) , AA and 1 / 2AA groups , respectively ) and recombinant human IGF 1 ( rhIGF 1 , 2 . 5 mg . kg body wt ( 1 ) . 24 h ( 1 ) ) infusion on the composition of the carcass and organs and on plasma insulin , IGF 1 , IGF binding protein 1 ( IGFBP 1 ) , and acid labile subunit ( ALS ) concentrations . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Insulin like growth factors ( IGF 1 , free IGF 1 and IGF 2 ) and insulin like growth factor binding proteins ( IGFBP 2 , IGFBP 3 , IGFBP 6 , and ALS ) in blood circulation . ^^^ Overall , IGF 1 , IGFBP 3 and ALS were slightly higher in females than in males . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Total IGF 1 level in serum is a sensitive index during growth hormone ( GH ) replacement therapy of adults , since GH stimulates the hepatic expressions of both insulin like growth factor ( IGF 1 ) and acid labile subunit ( ALS ) and the major part of IGF 1 in the circulation is found in a ternary complex together with ALS and IGFBP 3 . ^^^ It is not clarified , whether the IGF 1 levels within normal range for age is due to endogenous basal GH production being sufficient or other factors stimulating IGF 1 , IGFBP 3 or ALS expressions . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Body composition , IGF 1 , IGFBP 3 and ALS levels were measured before and after 3 months of rhGH therapy . ^^^ Body composition changed as expected most impressively in twin 1 ; twins 1 and 2 had low IGF 1 , IGFBP 3 and ALS prior to treatment with GH , but normal concentrations that were similar to those of their healthy twin were attained after 3 months of GH treatment . ^^^ Twin 3 had normal IGF 1 , IGFBP 3 and ALS concentrations before GH treatment , which were similar to those of her twin . ^^^ Insulin and GH have both been shown to stimulate hepatic production of IGF 1 and these results suggest that insulin may also be involved in the regulation of IGFBP 3 and ALS in vivo . ^^^ We conclude that clinical state , body composition and IGF 1 assessed together remain the best methods of monitoring GH replacement therapy and that measurements of IGFBP 3 and ALS do not confer any advantage over IGF I . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum concentrations of IGFBP 3 , 4 and 5 and acid labile subunit ( ALS ) were therefore examined in 20 children with growth hormone ( GH ) insensitivity before and after 6 months of therapy with recombinant human IGF 1 ( 80 or 120 micrograms / kg twice daily ) . ^^^ These findings indicate that GH is responsible for the regulation of serum levels of IGFBP 3 , 4 and 5 and ALS , and that IGF 1 does not directly regulate the concentrations of these circulating IGFBPs . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGFBP 3 ( Ad ) had similar affinities for IGF 1 and ALS and an approximately 25 % decreased affinity for IGF 2 compared to IGFBP 3 ( Pl ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF 1 and free IGF 1 concentrations increased , whereas IGF binding protein 3 ( IGFBP 3 ) and acid labile subunit ( ALS ) were unchanged during treatment . ^^^ There was no correlation between absorption or terminal half life of IGF 1 and IGFBP 3 or ALS , but negative correlations with IGF 1 clearance ( CL / F ) and volume of distribution ( V / F ) . ^^^ Positive correlations between both IGFBP 3 and ALS and IGF 1 maximal concentration ( C ( max ) ) and time of C ( max ) ( T ( max ) ) were observed . ^^^ Additionally , IGFBP 3 and ALS concentrations modulate the peak concentrations of IGF 1 achieved and correlate reciprocally with its V / F and CL / F , underscoring the critical importance of binding proteins in modulating the bioavailability of IGF 1 in vivo in humans . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Measurements of insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , and the acid labile subunit ( ALS ) are important in assessing the GH IGF axis . ^^^ As nearly all IGF 1 , IGFBP 3 , and ALS circulate in a GH dependent ternary protein complex , direct determination of the complex may be of significant analytical and clinical importance . ^^^ In pairwise mixed antibody evaluation , mAbs in G 2 and G 3 showed simultaneous binding to serum IGFBP 3 complexes in combination with an anti IGF 1 or an anti ALS antibody . ^^^ On this basis , two novel enzyme linked immunosorbent assays ( ELISAs ) involving IGFBP 3 / IGF 1 ( ELISA 1 ) and IGFBP 3 / ALS ( ELISA 2 ) recognition partners were developed , both demonstrating acceptable analytical performance characteristics . ^^^ IGFBP 3 complexes measured by ELISA 1 and 2 in samples from normal individuals and subjects with GH deficiency , acromegaly , and GH receptor deficiency more tightly correlated with IGF 1 , IGFBP 3 , and ALS than IGF 2 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Patient serum contained low levels of IGF 1 , IGFBP 3 and ALS , while the concentrations of IGFBP 2 and IGFBP 6 were markedly elevated . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Splanchnic exchange of insulin like growth factor binding protein 1 ( IGFBP 1 ) , IGF 1 and acid labile subunit ( ALS ) during normo and hyper insulinaemia in healthy subjects . ^^^ OBJECTIVE : The main source of circulating IGF 1 , insulin like growth factor binding protein 1 ( IGFBP 1 ) and acid labile subunit ( ALS ) is considered to be the liver , but their production rates have not been determined in healthy individuals . ^^^ Thus , the splanchnic exchange of IGFBP 1 , IGF 1 , ALS and glucose were studied . ^^^ There was a net splanchnic uptake of IGF 1 ( 7 + / 2 microg / min ) in the basal state , while no significant splanchnic exchange of ALS was found . ^^^ Insulin infusion influenced neither ALS nor IGF 1 splanchnic exchange . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Acute endurance type exercise increased serum GH , GH binding protein ( GHBP ) , total IGF 1 , IGF binding protein ( IGFBP ) 3 , and acid labile subunit ( ALS ) , each peaking at the end of exercise . ^^^ Recombinant human GH treatment ( 0 . 15 IU / kg 10 day ) for 1 week increased serum total IGF 1 , IGFBP 3 , and ALS , exaggerating the responses to exercise . ^^^ Total IGF 1 , IGFBP 3 , and ALS returned to baseline over 3 4 days . ^^^ In summary , 1 ) acute exercise transiently increased all components of the IGF 1 ternary complex , possibly due to mobilization of preformed intact complexes ; 2 ) GH pretreatment augmented the exercise induced changes in ternary complexes ; 3 ) postexercise IGFBP 1 increments may protect against delayed onset hypoglycemia ; 4 ) serum total IGF 1 , IGFBP 3 , and ALS may be suitable markers of GH abuse ; and 5 ) differences in disappearance times altered the sensitivity of each marker for detecting GH abuse . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Riluzole is available in amyotrophic lateral sclerosis ( ALS ) and the positive results of clinical trials with IGF 1 suggests that combination treatment of IGF 1 and riluzole in ALS remains to be determined . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We therefore measured IGF 1 , IGF 2 , IGF binding protein 1 ( IGFBP 1 ) , IGFBP 2 , IGFBP 3 , and acid labile subunit ( ALS ) in 27 GHD subjects ( aged 5 82 yr ) from an extended kindred in Northeast Brazil with an identical GHRH receptor mutation and in 55 indigenous controls ( aged 5 80 yr ) . ^^^ The most profound effects of GHD were on total IGF 1 , IGF 1 in the ternary complex , and ALS . ^^^ IGF 1 in the ternary complex was determined principally by concentrations of ALS in GHD and IGFBP 3 in controls , implying that ALS has greater GH dependency . ^^^ Similarly , in older adults the best separation was achieved with IGF 1 in the ternary complex , with free ALS being optimal in younger adults . ^^^ In particular , measurement of IGF 1 in the ternary complex may prove useful in the diagnosis of GHD in children and older adults , whereas free ALS may be more relevant to younger adults . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Specifically the reduced amount of GH released in pulses is found to be related to low circulating levels of IGF 1 , IGFBP 3 and acid labile subunit ( ALS ) , which suggests that a relative hyposomatotropism may participate in the pathogenesis of the wasting syndrome distinctively in the chronic phase of critical illness . ^^^ The relative hyposomatotropism seems at least in part of hypothalamic origin since the whole somatotropic axis has been found to be very responsive to continuous infusion of GH releasing peptide ( GHRP ) , administered alone or in combination with GH releasing hormone ( GHRH ) , as evidenced by reactivated pulsatile GH secretion followed by substantial increases in circulating levels of IGF 1 , IGFBP 3 and ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The Ati Negritos showed lower growth hormone binding protein ( GHBP ) , insulin like growth factor 1 ( IGF 1 ) , insulin like growth factor binding protein 3 ( IGFBP 3 ) , acid labile subunit ( ALS ) , zinc , albumin , ferritin , iron , iron saturation and much higher insulin like growth factor binding protein 2 ( IGFBP 2 ) and plasma transferrin concentrations . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The aim of our study was to determine the effects of 36 h fasting on 8 h diurnal GH , insulin and glucose levels as well as on basal IGF 1 , IGFBP 3 , acid labile subunit ( ALS ) , IGFBP 1 , GHBP and free fatty acid ( FFA ) levels . ^^^ STUDY DESIGN : In all subjects we studied the effects of 36 h fasting on 8 h daytime GH , insulin and glucose levels ( assay every 30 min from 0800 h to 1600 h ) as well as on basal IGF 1 , IGFBP 3 , ALS , IGFBP 1 , GHBP and FFA levels . ^^^ RESULTS : Before fasting , basal mean IGF 1 , IGFBP 3 and ALS levels in GHD were lower ( P < 0 . 0001 ) than in NS . ^^^ After fasting , both in GHD and NS basal IGF 1 , IGFBP 3 , ALS and GHBP levels did not change significantly . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum levels of free IGF 1 ( P =0 . 39 ) , IGF 2 ( P =0 . 54 ) , and of the acid labile subunit ( ALS ) of the ternary complex ( P =0 . 50 ) were similar during GH+ / OCT as compared with GH alone . ^^^ After 1 week off GH treatment , significantly lower levels of IGF 1 , IGF 2 , IGFBP 3 , and ALS were recorded ( P < 0 . 001 ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum IGF 1 , IGFBP 3 , and acid labile subunit ( ALS ) levels were low in patients compared with controls , with male patients revealing lower IGF 1 ( P = 0 . 01 ) and ALS ( P = 0 . 005 ) concentrations than female patients . ^^^ Correspondingly , circulating IGF 1 and ALS levels correlated positively with pulsatile ( but not with nonpulsatile ) GH secretion . ^^^ In conclusion , a paradoxical gender dissociation within the GH / IGF 1 axis is evident in protracted critical illness , with men showing greater loss of pulsatility and regularity within the GH secretory pattern than women ( despite indistinguishable total GH output ) and concomitantly lower IGF 1 and ALS levels . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
BACKGROUND / AIMS : In the circulation , insulin like growth factor 1 ( IGF 1 ) is bound in a trimeric complex of 150 kDa with IGF binding protein 3 ( IGFBP 3 ) and the acid labile subunit ( ALS ) . ^^^ Whereas circulating IGF 1 and IGFBP 3 are reported to be low in patients with chronic liver failure , the level of ALS has not been described in relation to hepatic dysfunction . ^^^ During a haemodynamic investigation , blood samples were collected from the hepatic vein and femoral artery , and the plasma concentrations of ALS , IGF 1 and IGFBP 3 were determined . ^^^ ALS correlated significantly with indicators of liver dysfunction , including the Child Turcotte score ( r= 0 . 69 , p < 0 . 0001 ) , IGF 1 ( r=0 . 82 , p < 0 . 0001 ) and IGFBP 3 ( r=0 . 74 , p < 0 . 0001 ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In adult animals , most circulating insulin like growth factor 1 ( IGF 1 ) and IGF 2 is sequestered in a 150 kDa complex composed of 1 molecule each of IGF , IGF binding protein 3 or 5 , and the acid labile subunit ( ALS ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum concentrations of ALS were also decreased by GH antagonism , but levels increased in some ( n = 2 ) , but not all , subjects upon administration of IGF 1 . ^^^ It remains to be determined whether IGF 1 directly affects hepatic synthesis and secretion of IGFBP 3 and what role IGF 1 has in the direct regulation of ALS in the monkey . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We conclude that ( 1 ) in contrast to humans and rats , ALS is the limiting factor for ternary complex formation in normal cats , ( 2 ) ALS concentrations increase in feline diabetes mellitus and , by promoting ternary complex formation , this leads to an increase in total IGF 1 concentrations , and ( 3 ) total IGF 1 concentrations may not be reliable in the diagnosis of acromegaly in diabetic cats . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The benefit of IGF 1 in amyotrophic lateral sclerosis ALS and its potential use in preventing motor neuron apoptosis in spinal cord injury dictates that studies of the presence and response of IGFBPs in that tissue be performed . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum ALS levels were significantly correlated with serum IGF 1 levels and IGFBP 3 levels . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
OBJECTIVES : Insulin like growth factor 1 ( IGF 1 ) has potent effects on motor neuron survival and is being studied as a possible therapeutic agent for ALS . ^^^ However , little is known concerning IGF 1 in the skin of patients with amyotrophic lateral sclerosis ( ALS ) . ^^^ The aim was to evaluate IGF 1 immunoreactivity of skin in patients with ALS . ^^^ METHODS : IGF 1 immunoreactivity of skin from 18 patients with ALS and 16 controls was examined . ^^^ RESULTS : IGF 1 immunoreactivity was markedly positive in the epidermis and dermal blood vessels and glands and was moderately positive in the reticular dermis in all patients with ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
This growth depression is associated with large decreases in the plasma concentrations of both IGF 1 and IGFBP 3 , indicating the critical role of ALS in the regulation of circulating levels of these proteins . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Therefore , ALS is required for postnatal accumulation of IGF 1 and IGFBP 3 but , consistent with findings supporting a predominant role for locally produced IGF 1 , is not critical for growth . ^^^ This model should be useful to determine whether presence of ALS is needed for other actions of liver derived IGF 1 and for maintenance of homeostasis in presence of high circulating levels of IGF II . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF 1 and IGFBP 3 concentrations were determined by radioimmunoassays and acid labile subunit ( ALS ) was measured by ELISA . ^^^ A shift in distribution of IGFBP 3 and IGF 1 in RA and OA synovial fluids ( RASynF , OASynF ) and an associated increase in ALS suggested the presence of 150 kDa ternary complexes . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF 1 circulates as a ternary complex with IGF binding protein 3 ( IGFBP 3 ) and the acid labile subunit ( ALS ) . ^^^ The changes in IGF 1 in each of the four studies paralleled the changes in both IGFBP 3 and ALS . ^^^ In conclusion , exogenous estrogens suppress serum IGFBP 3 and ALS in a route and dose dependent manner , which are in parallel with the effects on serum IGF 1 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Levels of IGF 1 , IGF 2 , IGF binding protein 3 ( IGFBP 3 ) and acid labile subunit ( ALS ) were low on admission , and in the 8 patients whose serum IGF 1 levels failed to increase over 30 days , levels of the other proteins also remained low , while IGFBP 3 proteolytic activity increased . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Insulin like growth factors ( IGFs ) circulate in plasma as part of a 150 kD complex that also contains IGF binding protein 3 ( IGFBP 3 ) , a protein that binds IGF 1 and IGF 2 with high affinity , and an acid labile subunit ( ALS ) that does not directly bind IGFs . ^^^ Significant correlations ( p < 0 . 001 ) were seen between total and free ALS concentrations and IGF 1 ( r = 0 . 50 and 0 . 60 , respectively ) , free IGF 1 ( r = 0 . 37 and 0 . 36 ) , IGF 2 ( r = 0 . 37 and 0 . 27 ) , IGFBP 1 ( r = 0 . 48 and 0 . 49 ) , IGFBP 2 ( r = 0 . 44 and 0 . 51 ) and IGFBP 3 ( r = 0 . 67 and 0 . 59 ) at all Tanner stages . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
At d 130 of fetal life , fetuses suffering from chronic undernutrition caused by placental insufficiency had lower expression of the ALS and IGF 1 genes than well nourished fetuses , but they did not have any changes in the expression of the IGF binding protein ( IGFBP ) 2 or IGFBP 3 genes . ^^^ The lower plane of nutrition decreased the expression of the ALS , IGF 1 , and GH receptor genes and increased the expression of the IGFBP 2 gene ; expression of the IGFBP 3 gene was not affected by nutrition at this stage of life . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Because growth is regulated by the GH insulin like growth factor ( IGF ) system , which may be altered in catabolic states , we studied serum IGF 1 , free IGF 1 , IGF 2 , the IGF binding proteins ( IGFBP 1 to 3 ) , and total and free acid labile subunit ( ALS ) levels in 26 prepubertal children with ALL at diagnosis ( n = 26 ) and 6 ( n = 21 ) , 12 ( n = 21 ) , 18 ( n = 21 ) , 24 ( n = 20 ) , 30 ( n = 16 ) , and 36 months ( n = 16 ) after beginning treatment to investigate the effects of disease and therapy on this system and its relationship with growth in these patients . ^^^ Serum IGF 1 , IGF 2 , IGFBP 3 , and total and free ALS levels were significantly decreased at diagnosis . ^^^ Normalization of IGF 2 and IGFBP 3 occurred 6 months after diagnosis , and normalization of IGF 1 and total and free ALS occurred 1 yr after terminating therapy . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We conclude that 1 ) males are significantly more responsive than females to exogenous GH ; 2 ) the increase in IGF 1 is more robust compared with those in IGFBP 3 and ALS ; 3 ) IGFBP 2 changes very little during GH treatment ; and 4 ) among IGF related substances , IGF 1 is the most specific marker of supraphysiological GH exposure . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The production by the liver of the three subunits of the growth hormone ( GH ) dependent 150 kDa complex ( IGF 1 , IGF binding protein 3 and acid labile subunit or ALS ) is primarily under the control of GH . ^^^ By limiting the formation of the 150 kDa complex , this reduction in circulating ALS might contribute to the rapid decline in serum IGF 1 observed in sepsis . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Body composition ( dual energy 10 ray absorptiometry ) , resting VO 2 ( indirect calorimetry ) , resting HR ( telemetry ) and serum IGF 1 , IGF 2 , IGFBP 3 and acid labile subunit ( ALS ) were measured at baseline , after 12 weeks of GH administration and , additionally in the GH group , 1 , 2 , 3 , 4 , 5 and 9 days after GH discontinuation . ^^^ Resting VO 2 and resting HR increased by 31 + / 3 . 6 % and 7 . 3 + / 1 . 9 per minute , respectively , in the GH group , where significant increases in serum IGF 1 , IGFBP 3 and ALS also were noted . ^^^ CONCLUSIONS : The increases in serum IGF 1 , IGFBP 3 , ALS and resting heart rate induced by 12 weeks of GH administration in elderly men returned to baseline levels within 2 3 days after GH discontinuation . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
STUDY DESIGN : We studied the effects of 36 h fasting on 8 h diurnal mean GH , insulin and glucose concentrations ( mGHc , mINSc and mGLUc ; assay every 30 min from 8 . 00 am to 4 . 00 pm ) as well as on IGF 1 , IGFBP 3 , ALS , IGFBP 1 , GHBP and free fatty acid ( FFA ) levels . ^^^ RESULTS : Before fasting , basal IGF 1 and ALS levels in OB were similar to those in NS and both were higher ( P < 0 . 001 ) than those in GHD . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF 1 circulates predominantly as a ternary complex with IGF binding protein 3 ( IGFBP 3 ) and the acid labile subunit ( ALS ) . ^^^ In the treatment of active acromegaly with the GH receptor antagonist pegvisomant , ALS showed a closer correlation with the change in ring size , measured as a clinical indicator of disease activity , than did IGF 1 or IGFBP 3 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Efficacy of radiotherapy in normalizing serum IGF 1 , acid labile subunit ( ALS ) and IGFBP 3 levels in acromegaly . ^^^ Serum GH and IGF 1 levels off medical therapy were measured in all patients ; ALS and IGFBP 3 were measured in 11 patients with normalization of IGF 1 concentrations . ^^^ ALS and IGFBP 3 concentrations paralleled IGF 1 levels in all patients studied . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
BACKGROUND / AIMS : In healthy adults , serum insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) and acid labile subunit ( ALS ) form a 150 kDa ternary complex under the control of growth hormone ( GH ) . ^^^ METHODS : Serum IGF 1 , IGFBP 3 , ALS , the 150 kDa ternary complex and IGFBP 3 proteolysis were all measured in six compensated and six decompensated cirrhotic patients and compared to six healthy controls . ^^^ RESULTS : Patients with compensated cirrhosis had decreased levels of IGF 1 ( 55 % ) , IGFBP 3 ( 64 % ) and ALS ( 53 % ) , and in the decompensated patients these levels were decreased even further : IGF 1 ( 32 % ) , IGFBP 3 ( 37 % ) and ALS ( 27 % ) compared to healthy controls . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In the circulation insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , and the acid labile subunit ( ALS ) form a 150 kDa ternary complex that is of importance for the regulation of IGF 1 bioactivity . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Serum IGF 1 and the acid labile subunit ( ALS ) were decreased by PN ( P < 0 . 001 ) and were not affected by GH during PN treatment . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
METHODS : We used an organotypic spinal cord model of glutamatergic degeneration in ALS to investigate whether IGF 1 and GDNF interact to enhance motor neuron survival , their trophic effect on choline acetyltransferase ( ChAT ) activity , and their effect on neurite outgrowth . ^^^ CONCLUSION : The results predict that IGF 1 combined with GDNF may provide a better therapy for the treatment of motor neuron disorders such as amyotrophic lateral sclerosis ( ALS ) and spinal muscular atrophy . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Candidate biochemical markers include insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) and the acid labile subunit ( ALS ) , and markers of bone remodelling . ^^^ Serum IGF 1 has the greatest utility during GH dose titration as it is more sensitive to changes in GH status than IGFBP 3 and ALS , and is also more sensitive to excessive GH replacement . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Indeed , researchers have shown that IGF 1 levels are of greater diagnostic value than other possible markers , such as IGF binding protein 3 ( IGFBP 3 ) and the acid labile subunit ( ALS ) . ^^^ Furthermore , IGF 1 levels , and possibly ALS levels , can be used to aid the diagnosis and monitoring of acromegaly . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Most serum IGF 1 associates with IGF binding protein 3 ( IGFBP 3 ) and another protein , the acid labile subunit ( ALS ) . ^^^ Like IGF 1 , serum concentrations of IGFBP 3 and ALS are tightly regulated by GH . ^^^ GH secretion ( both spontaneous and stimulated ) , IGF 1 , IGFBP 3 , and ALS have been assessed as potential biochemical markers for diagnosis of GH related disorders . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Various human recombinant neurotrophic molecules ( CNTF , BDNF , IGF 1 ) were administered to ALS patients . ^^^ IGF 1 slowed the progression of functional impairment in patients with ALS with no adverse effects . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Compared to wild type , male PPARalpha / mice had 40 % lower total fasting IGF 1 concentrations , decreased ALS and less IGFBP 3 ternary complex formation , but within 4 h of refeeding there was an increase in IGF 1 and IGFBP 3 ternary complex to values similar to controls . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Total IGF 1 , IGFBP 3 and ALS possess a higher PV ( neg ) for the clinical disease activity . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
RESULTS : Patients revealed suppressed pulsatile GH , TSH and LH secretion in the face of low serum concentrations of IGF 1 , IGFBP 3 and the acid labile subunit ( ALS ) ( P < 0 . 0001 each ) , thyroid hormones ( P < 0 . 0001 ) and total and estimated free testosterone ( P < 0 . 0001 ) levels , whereas free oestradiol ( E 2 ) estimates were normal . ^^^ GHRP 2 infusion reactivated GH secretion and normalized serum IGF 1 , IGFBP 3 and ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
RESULTS : Birth weight ( BW ) , birth length ( BL ) , ponderal index , head circumference ( HC ) , and cord serum levels of albumin , prealbumin , retinol binding protein ( RBP ) , total and free IGF 1 , IGF 2 , IGFBP 3 , acid labile subunit ( ALS ) , and leptin were significantly lower , whereas levels of IGFBP 1 , IGFBP 2 , and IL 6 were significantly higher in preterm than in term neonates ( P < 0 . 05 ) . ^^^ Total and free IGF 1 , ALS , and leptin had significantly positive correlations , whereas IGFBP 2 had a significantly negative correlation , with BW and BL in preterm plus term neonates . ^^^ Forward stepwise multivariate regression analysis showed that gestational age ( GA ) , IGFBP 2 , leptin , and free IGF 1 are significant predictors of BW ; GA , IGFBP 2 , ALS , transferrin , and leptin are significant predictors of BL ; and GA and free IGF 1 are significant predictors of HC in preterm and term neonates . ^^^ CONCLUSIONS : Our results suggest that IGF 1 , IGF 2 , IGFBP 2 , ALS , and leptin play important roles in intrauterine growth . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Like IGF 1 and IGFBP 3 , serum levels of ALS depend on growth hormone ( GH ) . ^^^ We also measured the levels of serum IGF 1 and IGFBP 3 in these patients to compare the utility of ALS with IGF 1 and IGFBP 3 as a marker of GH secretion . ^^^ Serum ALS was measured by radioimmunoassay ( RIA ) kit , and serum IGF 1 and IGFBP 3 were measured by immunoradiometric assay ( IRMA ) kits in 56 patients with adult GHD ( adult onset ( AO ) / child onset ( CO ) , 13 / 43 ) and 43 patients with acromegaly . ^^^ These data suggested that measurement of ALS offers no advantage over measurements of serum IGF 1 and IGFBP 3 . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Liver IGF 1 deficient ( LID ) mice and ALS knockout ( ALSKO ) mice exhibited relatively normal growth and development , despite having 75 % and 65 % reductions in serum IGF 1 levels , respectively . ^^^ Thus , the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF 1 is necessary for normal bone growth and suggests that IGF 1 , IGFBP 3 , and ALS play a prominent role in the pathophysiology of osteoporosis . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The aim of the study was to evaluate serum acid labile subunit ( ALS ) concentrations and their relationship with other parameters of the human ternary IGF 1 binding protein ( IGFBP ) complex in girls with central precocious puberty ( CPP ) before and after pharmacological arrest of puberty . ^^^ We studied serum ALS , free IGF 1 , total IGF 1 , IGFBP 3 levels and IGFBP 3 protease activity in 13 girls , aged 1 . 6 7 . 8 yr ( mean , 5 . 9 + / 2 . 2 ) , diagnosed as having CPP before and after 6 and 12 months of GnRH analog ( GnRHa ) therapy . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
METHODS : Viral load , CD 4 count , interleukin 6 ( IL 6 ) , growth hormone , insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 3 ( IGFBP 3 ) , acid labile subunit ( ALS ) , IGFBP 3 proteolysis , osteocalcin in blood and N terminal telopeptide of type 1 collagen in urine were determined . ^^^ Low IGF 1 was found in only six children , who had low CD 4 count and high IL 6 levels , with normal levels of IGFBP 3 and ALS , absent IGFBP 3 proteolysis and decreased bone mineral density , irrespective of viral load or growth . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
The concentrations of the following markers were determined in relevant serum samples : IGF 1 , IGFBP 3 , ALS , PIIINP , PINP , osteocalcin , and leptin . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Despite GH hypersecretion , serum IGF 1 , IGFBP 3 , and ALS levels have all been reported to be low in patients with anorexia nervosa ( AN ) , while the degree of ternary complex formation in AN is unknown . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We characterized the GH IGF 1 axis by analyzing the individual components of the axis ( GH , IGF 1 , IGF binding protein 3 [ IGFBP 3 ] , acid labile subunit [ ALS ] ) and the corresponding ratios ( GH / IGF 1 , GH / IGFBP 3 , and GH / ALS ) and verified the links with circulating proinflammatory cytokines ( TNF alpha , IL 1beta , and IL 6 ) , in 34 patients with CLD and 12 healthy controls . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Somatomedin circulates in plasma in complex with a family of binding proteins . 85 95 % of total IGF 1 is found in the complex consisting of IGF 1 , binding protein 3 and ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
We examined the impact of cirrhosis on hepatic mRNA and serum protein levels for the GH receptor ( GHR ) / binding protein ( GHBP ) , IGF 1 , IGF binding protein ( IGFBP ) 3 and the acid labile subunit ( ALS ) . ^^^ Hepatic IGF 1 and ALS mRNA were significantly decreased by 84 and 68 % , respectively , in parallel with serum protein , suggesting transcriptional regulation . ^^^ CONCLUSIONS : The decreased mRNA and serum levels for the GH dependent , hepatocyte produced proteins IGF 1 and ALS confirm the importance of GH receptor loss to the GH resistance of cirrhosis . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Malnutrition suppresses ALS and IGF 1 expression in a development dependent manner . ^^^ Furthermore , hepatic ALS and IGF 1 mRNA showed no age differential response to fasting and refeeding , suggesting posttranscriptional regulation . ^^^ We hypothesize that development dependent regulation of ALS and IGF 1 during refeeding may involve a posttranscriptional hepatic response that is not GH dependent . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
RESULTS : Basal serum levels of IGF 1 ( P < 0 . 0001 ) and IGFBP 3 ( P < 0 . 01 ) declined with age , but serum acid labile subunit ( ALS ) levels did not ( P = 0 . 2 ) . ^^^ However , the increment in IGF 1 , IGFBP 3 and ALS in response to GH did not decline with age . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF 1 , acid labile subunit ( ALS ) , IGFBP 1 and 3 mRNA levels were determined by Northern blot analysis . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Retrograde viral delivery of IGF 1 prolongs survival in a mouse ALS model . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
IGF 1 circulates in free , ternary [ IGF 1 + IGFBP 3 + acid labile subunit ( ALS ) ] , and binary ( IGF 1 + IGFBP ) molecular complexes , and the relative proportions regulate IGF 1 extravascular shifting and bioavailability . ^^^ Components of the IGF 1 system ( total and free IGF 1 ; IGFBP 1 , 3 , and ALS ; nonternary IGF 1 and IGFBP 3 ) , biomarkers of metabolic and nutritional status ( transferrin , ferritin , prealbumin , glucose , free fatty acids , glycerol , beta hydroxybutyrate ) , and body composition were measured in 12 men ( 22 + / 3 yr , 87 + / 8 kg , 183 + / 7 cm , 20 + / 5 % body fat ) on days 1 , 3 , and 4 during a control and experimental ( Exp ) period . ^^^ IGF 1 and IGFBP 3 were measured by immunoassay before and after immunoaffinity depletion of ALS based complexes ( i . e . , ternary complex removal ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In the present study , we used the SOD 1 ( G93A ) mutant transgenic mice as an in vivo model of ALS and performed immunohistochemical studies to investigate the changes of insulin like growth factor 1 ( IGF 1 ) receptor in the central nervous system . ^^^ The present study provides the first evidence that IGF 1 receptor immunoreactivity was increased in reactive astrocytes in the central nervous system of SOD ( G93A ) transgenic mice , suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Dominant negative STAT5b completely inhibited GH stimulated transcription of genes encoding the growth promoting proteins IGF 1 , IGF binding protein 3 ( IGFBP 3 ) , and acid labile subunit ( ALS ) , which comprise the major circulating IGF 1 complex , and blocked expression of the GH inhibitors SOCS 1 , SOCS 2 , and CIS , but had little effect on induction of SOCS 3 . ^^^ Constitutive active STAT5b stimulated robust transcription of IGF 1 , ALS , and IGFBP 3 in the absence of hormone but did little to modify GH mediated activation of SOCS family genes . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
In training subjects GH treatment increased GH , IGF 1 , IGFBP 3 and ALS , and decreased IGBP 2 . ^^^ After cessation of treatment IGF 1 , IGFBP 3 and ALS approached basal values between 49 and 96 h . ^^^ In conclusion , increases in IGF 1 , IGFBP 3 , ALS , PIIIP and ICTP are all indicative of recent GH abuse or of acromegaly . . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
To understand the role of the GH / IGF 1 axis in liver regeneration , we performed partial hepatectomies in three groups of mice : GH antagonist ( GHa ) transgenic mice , in which the action of GH is blocked ; liver IGF 1 deficient mice that lack IGF 1 specifically in the liver and also lack the acid labile subunit ( ALS ; LID+ALSKO mice ) , in which IGF 1 levels are very low and GH secretion is increased ; and control mice . ^^^
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Serum insulin like growth factor 1 ( IGF 1 ) , acid labile subunit ( ALS ) and IGF binding protein 1 ( IGFBP 1 ) levels were determined by specific radioimmunoassay methods . ^^^ Parenteral nutrition , but not enteral nutrition , increased muscle ( P = 0 . 02 ) and liver ( P < 0 . 001 ) Ks , IGF 1 ( P < 0 . 001 ) and ALS levels ( P < 0 . 001 ) , whereas both parenteral and enteral nutrition reduced IGFBP 1 levels ( P < 0 . 001 ) . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
MEASUREMENTS : We analysed the strength and independence of associations of angiographically assessed presence of CHD with BMI , systolic and diastolic blood pressure , total , high density lipoprotein ( HDL ) and LDL cholesterol , triglycerides , lipoprotein ( a ) , apolipoproteins A 1 and B , total and free IGF 1 , IGF 2 , IGFBP 1 , IGFBP 3 , IGFBP 5 , acid labile subunit ( ALS ) , insulin , C peptide , testosterone , DHEAS and sex hormone binding globulin . ^^^ RESULTS : Using multivariate statistical analysis , the presence of CHD had significant positive associations with total IGF 1 , IGFBP 5 , ALS and IGFBP 3 . ^^^
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When mated with an acid labile subunit ( ALS ) gene deleted mouse they also show osteopenia suggesting that circulating IGF 1 levels play a significant role in bone formation . ^^^
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Muscle expression of a local Igf 1 isoform protects motor neurons in an ALS mouse model . ^^^
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This review details the general physiology , biochemistry and molecular biology of insulin like growth factor 1 ( IGF 1 ) , a pleiotropic factor , and the only one to date showing beneficial effects in a prototypic neurodegenerative disease , amyotrophic lateral sclerosis ( ALS ) . ^^^ The preclinical rationale for IGF 1 use in treating patients with ALS stems from the fact that this molecule has endocrine , paracrine and autocrine effects on cells and acts through a receptor tyrosine kinase that is structurally and functionally similar to the insulin receptor . ^^^ In order to explain why this trophic factor , unlike ciliary neurotrophic factor ( CNTF ) and brain derived neurotrophic factor ( BDNF ) , was found to have efficacy in large scale clinical trials in ALS patients , evidence is offered that IGF 1 affects all components of the motor unit : spinal cord motor neuron , axon , neuromuscular synapse and muscle fiber . ^^^
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In 19 girls and 18 boys , the levels of IGF 1 , free IGF 1 , IGF 2 , acid labile subunit ( ALS ) and IGF binding proteins ( IGFBP ) 2 to 6 were measured before and 3 6 months after the start of therapy ( group 1 ) . ^^^
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IGF 1 , IGFBP 3 and ALS are GH dependent peptides and their production is disturbed in states of GH insensitivity . ^^^ This chapter explores the relative degrees of IGF 1 , IGFBP 3 and ALS deficiency across the spectrum of GH insensitivity . ^^^ In classical GH insensitivity syndrome ( GHIS ) , known as Laron syndrome , due to GH receptor ( GHR ) deficiency , serum IGF 1 , IGFBP 3 and ALS are severely reduced with inability to produce these peptides during an IGF 1 generation test . ^^^ IGF 1 , IGFBP 3 and ALS were significantly higher ( p < 0 . 05 ) in pubertal compared with pre pubertal subjects in the same series . ^^^ In summary , assessment of IGF 1 , IGFBP 3 and ALS contributes to diagnosis in GH insensitivity states . ^^^
Interacting proteins: P35858 and P05019 Pubmed SVM Score :0.0
Evidence that IGF 1 rescues motor neurons has led to clinical trials of human recombinant IGF 1 in ALS patients . ^^^ However , systemic delivery of human recombinant IGF 1 in these trials did not lead to beneficial clinical effects in ALS patients and may be due through inactivation of IGF 1 by binding to IGF binding proteins ( IGFBPs ) , and or limited delivery of IGF 1 to motor neurons . ^^^ Recently it was shown that both IGF 1 receptors and IGFBPs were increased on motor neurons of ALS patients and free levels of IGF 1 were decreased by 50 % . ^^^
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We demonstrated that the level of IGF 1 and ALS mRNAs is dramatically decreased in both young and aged dwarf livers , transcripts encoding IGF IR and IGFBP 1 are elevated in young dwarfs , but normalize to control levels in aged dwarf livers while transcripts encoding IGFBP 3 are elevated only in aged controls . ^^^
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To examine the possible effectiveness of IGF 1 in a mouse model of familial ALS , transgenic mice expressing human Cu / Zn superoxide dismutase ( SOD 1 ) with a G93A mutation were treated by continuous IGF 1 delivery into the intrathecal space of the lumbar spinal cord . ^^^ Taken together , the results suggest that direct administration of IGF 1 into the intrathecal space may have a therapeutic benefit for ALS . . ^^^
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Recently , two drugs , namely riluzole and recombinant human insulin like growth factor 1 ( IGF 1 ) , have been reported to benefit patients with ALS by improving survival or slowing disease progression . ^^^
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These complexes are referred to as binary complexes consisting of IGF 1 or IGF 2 and one IGFBP , or as ternary complexes each consisting of either of IGF 1 or IGF 2 , IGFBP 3 or 5 , and an acid labile subunit known as ALS . ^^^ The plasma concentrations of IGF 1 and IGFBP 3 were markedly reduced both in ALS KO mice and in the ALS deficient patients . ^^^ Phenotypic features of complete ALS deficiency , that are very similar in mouse and human , include : a ) the inability to form ternary complex , b ) the small growth impairment in spite of the marked reduction in circulating IGF 1 , and c ) the reduction in BMD . ^^^ These findings underlie the important physiological role of ALS in the maintenance of the circulating IGF 1 reservoir . ^^^
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The aims of this study were : ( 1 ) to examine the effect of different therapeutic modalities ( transsphenoidal surgery , TSS ; radiotherapy , RT ; medical treatment with somatostatin analogues , SSA ) on the daily spontaneous GH secretory pattern ( day curve ) ; and ( 2 ) to determine the relationship between the characteristics of the GH secretory pattern and the circulating concentration of IGF 1 , acid labile subunit ( ALS ) and IGFBP 3 . ^^^ IGF 1 , IGFBP 3 and ALS were measured in basal conditions . ^^^ No significant differences were observed with regard to the mean GH , IGF 1 , ALS or IGFBP 3 among the different treatment groups . ^^^
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IGF 1 , IGFBP 3 , the acid labile subunit ( ALS ) , N terminal propeptide of type 1 collagen ( PINP ) , C terminal telopeptide of type 1 collagen ( ICTP ) and N terminal propeptide of type 3 collagen ( PIIINP ) were measured in samples collected at baseline ( two samples ) , after 10 , 22 and 24 days of r HuEPO treatment and at the end of the 4 week wash out period . ^^^ There was no significant treatment effect of r HuEPO compared to baseline on IGF 1 , IGFBP 3 , ALS , PINP , ICTP or PIIINP . ^^^
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To study this further , we evaluated mRNA levels of pituitary GH , and of IGF 1 , GH receptor ( GHR ) and acid labile subunit ( ALS ) in liver and skeletal muscle of male C3H and B 6 strains . mRNA levels of hepatic IGF 1 paralleled serum IGF 1 levels , whereas pituitary GH mRNA expression was significantly lower in C3H than B 6 . ^^^
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OBJECTIVE : The objective of this study was to define the optimal time point of postoperative evaluation by serial measurements of glucose suppressed GH levels [ oral glucose tolerance test ( OGTT ) ] and the GH dependent parameters IGF 1 , free IGF 1 , acid labile subunit ( ALS ) , and GH binding protein ( GHBP ) . ^^^ MAIN OUTCOME MEASURES : The main outcome measures were OGTT results at 1 , 2 , 3 , 8 , and 12 wk after TA ; weekly measured GH , ( free ) IGF 1 , ALS , and GHBP levels up to 12 wk ; and total IGF 1 levels measured at 52 wk . ^^^ Free IGF 1 and ALS levels may have an additional value in the postoperative assessment of disease activity . . ^^^
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We performed a double blind clinical trial to assess the effect of intrathecal administration of IGF 1 on disease progression in patients with ALS . ^^^ METHODS : Nine patients with ALS were randomly assigned to receive either a high dose ( 3 microg / kg of body weight ) or low dose ( 0 . 5 microg / kg of body weight ) of IGF 1 every 2 weeks for 40 weeks . ^^^ The intrathecal administration of IGF 1 had a modest but significant beneficial effect in ALS patients without any serious adverse effects . ^^^ DISCUSSION : Intrathecal IGF 1 treatment could provide an effective choice for ALS although further studies in more patients are needed to confirm its efficacy and optimize dosages of IGF 1 . . ^^^
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The role of insulin like growth factor 1 ( IGF 1 ) in amyotrophic lateral sclerosis ( ALS ) and its mechanism of action are important from both pathogenic and therapeutic points of view . ^^^
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GH , IGF 1 , IGF binding protein ( IGFBP ) 3 , and acid labile subunit ( ALS ) levels were evaluated before and during therapy . ^^^ The association of low IGF 1 and ALS with normal IGFBP 3 levels could explain growth impairment of M+ children and could suggest a GH resistance by a late postreceptor signaling defect . . ^^^
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IGF 1 , insulin like growth factor binding protein ( IGFBP ) 3 and acid labile subunit ( ALS ) levels were measured at baseline and 24 h after GH administration . ^^^
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However , most of the circulating IGF 1 associates with a high molecular weight complex approximately 150 KDa consisting of IGFBP 3 and the acid labile subunit ( ALS ) ADDIN . ^^^
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Absence of human and also mouse ALS leads to decreased IGF 1 levels in circulation and causes mild growth retardation . ^^^
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Because IGF 1 , which circulates as part of a ternary complex with IGF binding protein ( IGFBP ) 3 and acid labile subunit ( ALS ) , mediates the growth promoting effects of GH , IGFD is associated with severe growth failure in humans . ^^^ CONCLUSIONS : ALS is critical for maintaining normal serum concentrations of IGF 1 and IGFBP 3 , most likely by prolonging the half lives of both proteins . ^^^
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Patients were evaluated by the determination of baseline ( fasting ) IGF 1 , ALS and GHBP and of glucose and GH during OGTT . ^^^
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We generated IGF 1 deficient mice by gene deletions of IGF ternary complex components including : ( 1 ) liver specific deletion of the IGF 1 gene ( LID ) , ( 2 ) global deletion of the acid labile ( ALS ) gene ( ALSKO ) , and ( 3 ) both liver IGF 1 and ALS inactivated genes ( LA ) . ^^^
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We report on a 10 yr old Caucasian girl affected by Costello syndrome with fasting hypoglycemia and short stature , associated low circulating levels of acid labile subunit ( ALS ) , relatively low levels of IGF 1 and IGFBP 3 , and normal IGF 2 , mostly circulating in a binary complex with IGFBP 2 and 6 instead of in a 150 kDa ternary complex . ^^^ The reduced ALS concentration and the consequent impaired formation of the circulating 150 kDa ternary complex can induce an accelerated clearance rate of IGF peptides and of IGFBP 3 , contributing to the decreased IGF 1 growth promoting activity in our patient . ^^^
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In WT mice , the GH antagonist pegvisomant ( Peg ) suppressed the transcription of endogenous IGF 1 and acid labile subunit ( ALS ) genes with no effect on IGF binding protein 3 ( IGFBP 3 ) mRNA . ^^^ Consequently , Peg induced GH deficiency in WT mice severely reduced ALS , IGF 1 , and IGFBP 3 in the circulation and caused a severe growth deficit . ^^^
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The impact of GH deficiency and rhGH replacement therapy on IGF 1 , IGFBP 3 and ALS levels has been widely studied . ^^^
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IGF 1 circulates predominantly in multi protein complexes consisting of one molecule each of IGF 1 , IGF binding protein 3 and the acid labile subunit ( ALS ) . ^^^ Recent studies in the mouse have shown that absence of ALS results in accelerated turnover and severely depressed concentration of plasma IGF 1 . ^^^ These observations suggest that reduced plasma ALS could be a second factor contributing to the fall of plasma IGF 1 in peri parturient cows . ^^^
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RESULTS : All the patients with certain GHD had low ( < or = 2 z score ) plasma concentrations of IGF 1 and ALS , but only 35 . 1 % had low IGF 2 , and 48 . 6 % had low IGFBP 3 . ^^^ All the patients but three ( 83 . 3 % ) with transient GHD had low IGF 1 , but only 44 . 4 % had low ALS , and only one had low IGF 2 or IGFBP 3 . ^^^ CONCLUSIONS : All the patients with certain GHD had both IGF 1 and ALS z scores < or = 2 , unlike those with transient GHD , and idiopathic or extreme short stature . ^^^
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Other agents ( ceftriaxone , minocycline , ONO 2506 , and IGF 1 polypeptide ) are already in phase 3 trials involving large numbers of patients with ALS . ^^^
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Pregnancy induced changes in insulin like growth factor 1 ( IGF 1 ) , insulin like growth factor binding protein 3 ( IGFBP 3 ) , and acid labile subunit ( ALS ) in patients with growth hormone ( GH ) deficiency and excess . ^^^ BACKGROUND : Under most circumstances with altered growth hormone ( GH ) secretion , the changes of insulin like growth factor 1 ( IGF 1 ) , insulin like growth factor binding protein 3 ( IGFBP 3 ) , and acid labile subunit ( ALS ) are in parallel . ^^^ The aim of the present study was to compare the effects of pregnancy in a hypopituitary patient with those of pregnancy in an acromegalic patient on IGF 1 , IGFBP 3 , and ALS . ^^^ METHODS AND RESULTS : IGF 1 and ALS were low before pregnancy in the hypopituitary patient under glucocorticoid and thyroxine treatment . ^^^ Gonadotropin treatment allowed her to become pregnant ; IGF 1 and ALS levels rose in the second half of pregnancy and fell again after delivery . ^^^
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The correlation of the IGF 1 , IGFBP 3 , and ALS generation test to height velocity after 6 months of recombinant growth hormone therapy in girls with Turner syndrome . ^^^ Levels of IGF 1 and IGFBP 3 were measured before and 5 , 30 and 90 days after starting hGH ( 0 . 05 mg / kg / day ) , ALS levels were measured only prior and after 5 days . ^^^ Basal ALS values correlated to height velocity SDS and IGF 1 and IGFBP 3 , after 90 days , correlated to height velocity . ^^^
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However , measurements of IGF 1 and its binding proteins , as well as GH and its binding proteins , can help us to focus our analysis of patients suspected to have genetic abnormalities on the GH receptor , IGF 1 , its receptor , IGFALS , or intracellular signalling proteins such as STAT5b or ERK . ^^^
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We genotyped 23 common single nucleotide polymorphisms in IGF 1 , IGFBP 1 , IGFBP 3 and IGFALS , and measured serum levels of IGF 1 and IGFBP 3 in samples of cases and controls . ^^^
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