Regulation and localization of the insulin-like growth factor system in small bowel during altered nutrient status

1995 ◽  
Vol 268 (4) ◽  
pp. G631-G640 ◽  
Author(s):  
D. E. Winesett ◽  
M. H. Ulshen ◽  
E. C. Hoyt ◽  
N. K. Mohapatra ◽  
C. R. Fuller ◽  
...  
Keyword(s):  
Growth Factor ◽  
Small Bowel ◽  
Lamina Propria ◽  
Elemental Diet ◽  
Nutrient Status ◽  
Insulin Like Growth Factor ◽  
Nutrient Regulation ◽  
Igf I ◽  
Ad Libitum ◽  
Igfbp 3

Insulin-like growth factor-I (IGF-I) may regulate small bowel growth. Analyses here in ad libitum-fed, fasted, and refed rats demonstrate that during fasting and refeeding changes in jejunal mass correlate with changes in serum IGF-I and jejunal IGF-I mRNAs. These data indicate that circulating and locally expressed IGF-I contribute to nutrient regulation of jejunal mass. During refeeding, jejunal IGF binding protein 3 (IGFBP-3) mRNA abundance was reduced relative to that of IGF-I, possibly amplifying enterotrophic actions of IGF-I. Localization of IGFBP-3 to subepithelial cells in lamina propria of jejunum indicates that IGFBP-3 derived from lamina propria may modulate IGF-I action on adjacent epithelium. Ileum differed from jejunum in that refeeding did not increase bowel mass or IGF-I mRNA to ad libitum values. Differences in exposure to luminal nutrient may underlie distinct responses of the two segments. Rats fed elemental diet intravenously showed reduced jejunal mass but not reduced jejunal IGF-I mRNA compared with rats fed oral elemental diet. Elemental nutrient given intravenously or orally therefore does not differ in effects on jejunal IGF-I expression. Complex luminal nutrient may, however, regulate jejunal IGF-I expression.

Effect of sodium selenite on growth, insulin-like growth factor-binding proteins and insulin-like growth factor-I in rats

1995 ◽  
Vol 145 (1) ◽  
pp. 105-112 ◽  
Author(s):  
H Grønbæk ◽  
J Frystyk ◽  
H Ørskov ◽  
A Flyvbjerg
Keyword(s):  
Growth Factor ◽  
Sodium Selenite ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Selenium Treatment ◽  
Group A ◽  
Ad Libitum ◽  
Group B ◽  
Igfbp 3

Abstract Selenium is an essential trace element although at higher doses it is also known to be a toxic agent causing a wide range of symptoms including growth retardation. In order to investigate the effect of sodium selenite on growth, insulin-like growth factor-binding proteins (IGFBPs) and insulin-like growth factor-I (IGF-I), 30 male Wistar rats were randomized into three groups. Group A was treated with sodium selenite in the drinking water (3·3 mg selenium/l). Group B was ad libitum fed with free access to standard fodder and tap water and group C was pair fed relative to the selenium-treated rats. Serum IGF-I and IGFBPs were determined on days 0, 14 and at the end of the study on day 35. Selenium-treated rats had significantly lower body weights compared with group B rats on day 9 and group C rats on day 14 (P<0·05). Tibia length was measured at the end of the study and no difference was observed between groups B and C (3·77 ± 0·04 cm vs 3·60±0·02 cm); however, selenium-treated rats had significantly shorter tibia lengths (3·46±0·03 cm) compared with rats in groups B (P<0·001) and C (P<0·05). Selenium treatment induced a significant reduction in circulating IGF-I by the end of the study compared with ad libitum and pair fed rats (P<0·05). Serum subjected to Western ligand blots showed four distinct IGFBP bands with apparent relative molecular weights of 38–47 kDa (doublet) (IGFBP-3), 30 kDa (IGFBP-1 and/or IGFBP-2) and 24 kDa (IGFBP-4). At the end of the study a significant reduction in IGFBP-3 was observed in group A compared with groups B and C (P<0·05). Selenium treatment also caused a reduction in IGFBP-1 and/or IGFBP-2 compared with ad libitum fed rats; in addition, a reduction was observed in pair fed controls. In conclusion, sodium selenite treatment leads to growth retardation accompanied by reduced circulating levels of IGF-I, IGFBP-3, and IGFBP-1 and/or IGFBP-2. The reduction in IGF-I and IGFBP-3 could not be attributed to reduced caloric intake but seems to be a specific action of selenium. Journal of Endocrinology (1995) 145, 105–112

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4

1993 ◽  
Vol 136 (1) ◽  
pp. 91-104 ◽  
Author(s):  
L. R. Donahue ◽  
W. G. Beamer
Keyword(s):  
Body Composition ◽  
Growth Factor ◽  
Gh Deficiency ◽  
Body Water ◽  
Insulin Like Growth Factor ◽  
Gh Therapy ◽  
Factor I ◽  
Igf I ◽  
Body Compartments ◽  
Igfbp 3

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104

scholarly journals Genetic Determinants of Circulating Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (BP)-1, and IGFBP-3 Levels in a Multiethnic Population

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Genetic Determinants ◽  
Igf I ◽  
Igf Binding ◽  
Multiethnic Population ◽  
Igf Binding Protein ◽  
Igfbp 3

Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration

1996 ◽  
Vol 271 (5) ◽  
pp. G866-G875 ◽  
Author(s):  
T. R. Ziegler ◽  
M. P. Mantell ◽  
J. C. Chow ◽  
J. L. Rombeau ◽  
R. J. Smith
Keyword(s):  
Growth Factor ◽  
Small Bowel ◽  
Dna Content ◽  
Bowel Resection ◽  
Synergistic Effects ◽  
Intestinal Adaptation ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Insulin Like Growth Factor ◽  
Igf I

Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gln) or by administration of insulin-like growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gln and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gln or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gln and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gln diet. Ileal DNA content was highest when IGF-I was administered together with Gln supplementation. Combined IGF-I plus Gln synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gln than observed when IGF-I or Gln was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gln feeding. In contrast, dietary Gln, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gln have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.

Measurement of Human Igf-II Using Sephacryl Extraction: A Rapid and Reliable Assay Method

1996 ◽  
Vol 33 (3) ◽  
pp. 201-208 ◽  
Author(s):  
Barbara H Mason ◽  
Michele A Tatnell ◽  
Ian M Holdaway
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Complete Removal ◽  
Assay Method ◽  
Insulin Like Growth Factor ◽  
Serum Concentrations ◽  
Igf Binding Proteins ◽  
Factor Ii ◽  
Igf I ◽  
Igfbp 3

Measurement of insulin-like growth factor II (IGF-II) in human serum is complicated by the presence of IGF binding proteins and usually involves cumbersome extraction procedures followed by radioimmunoassay. We have utilized an extraction process developed for measuring insulin-like growth factor II in ovine serum using Sephacryl HR100, and have applied this to the extraction of human samples followed by radioimmunoassay for human IGF-II. The assay yielded 98% recovery of unlabelled IGF-II, parallelism between dilutions of eluate and the standard curve, complete removal of binding proteins and near-complete removal of IGF-I, and intra- and interassay coefficients of variation of 5% and 9%, respectively. The normal range for serum IGF-II in women was 490–1056 μg/L, and IGF-II levels were positively correlated with serum concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) but not with IGF-I levels. Mean serum concentrations of IGF-II were reduced below normal in a number of hypopituitary patients and children with short stature and IGF-II concentrations in these subjects correlated positively with IGF-I and IGFBP-3. In acromegalic patients IGF-II levels were usually normal and were negatively correlated with IGF-I concentrations. From our experience with the above results the present assay appears particularly suitable for clinical measurements and research projects where high sample throughput is required.

Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature

2021 ◽  
Vol 185 (5) ◽  
pp. 629-635
Author(s):  
Aristeidis Giannakopoulos ◽  
Alexandra Efthymiadou ◽  
Dionisios Chrysis
Keyword(s):  
Growth Factor ◽  
Short Stature ◽  
Ternary Complex ◽  
Final Height ◽  
Hormone Deficiency ◽  
Receiver Operating Curve ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Stimulation Tests ◽  
Igfbp 3

Objective The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Design Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. Results All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Conclusion Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

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