Common mechanism of action of somatomedin and insulin on fat cells. Further evidence.
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Biomedical subjects
Publications and source records attributed to D R Clemmons.
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The action of growth hormone on skeletal tissue is mediated through somatomedin, a low molecular weight peptide found in serum. This peptide, formerly known as "sulfation factor" or "thymidine factor," produces marked insulin-like effects in various target tissues. Since at least some of the metabolic effects of insulin on target cells are initiated by a highly specific interaction with receptors on cell membranes, this study was undertaken to determine whether somatomedin might interact with the same binding sites. It was found that somatomedin, at physiological concentrations, competes with (125)I-labeled insulin for receptor sites on isolated fat cells, liver membranes, and isolated chondrocytes, and that the relative binding affinities of insulin and somatomedin reflect the in vitro biological potencies of the two hormones in these tissues. This is the first demonstration of a peptide other than insulin, proinsulin, or derivatives of insulin competing for insulin-binding sites, and implies a structural, as well as a functional, homology between somatomedin and insulin. Somatomedin may be only one of a larger group of homologous pleiotypic peptides with different target organ specificities.
Insulin-like growth factor (IGF) I and II are synthesized within the placenta and are believed to play an important role in the regulation of placental growth and endocrine function. IGF bioavailability is determined at a cellular level by several specific binding proteins (IGF BPs), which are widely but selectively distributed in all developing tissues. We have used immunohistochemistry to localize IGF I and II peptides, and IGF BP-1, -2, and -3 in human placentae, fetal membranes and umbilical cord at 6-8 weeks after therapeutic termination and at term after spontaneous delivery. Primary antisera were directed against human IGF I, human IGF BP-1, bovine IGF BP-2, and human IGF BP-3 respectively. Immunoreactive IGF BP-2 was found in association with the syncytiotrophoblast, intermediate trophoblasts of the fetal villi and chorion, amnion and decidua; while weaker staining was seen in some but not all cytotrophoblasts. A similar but less intense staining pattern was observed for IGF BP-1 and IGF peptides in placenta and amnio-chorion. Strong immuno-staining for IGF BP-1 was seen in decidual cells. No immunoreactive IGF BP-3 was found in placenta or membranes. A co-distribution of IGF BP-2, BP-1 and IGF peptides in placenta suggests a role for these IGF BPs in determining the localization of the IGFs for actions on target tissues.
We have attempted to determine the relative importance of dietary intake of protein and energy in restoring plasma immunoreactive somatomedin-C (Sm-C) concentrations after fasting. Ten healthy human volunteers were fasted for 5 days, then divided into two refeeding groups. One group (variable energy) was refed 1.0 g protein/kg ideal body weight, and in 9-day sequences, 11, 18 and 25 kcal of energy/kg. The other group (variable protein) was given 35 kcal energy/kg, and in 9-day sequences, 0.2, 0.4, and 1.0 g protein/kg. When subjects were refed the variable energy diets there was no significant increase in Sm-C at 11 kcal/kg (0.47 +/- 0.13 to 0.45 +/- 0.12 U/ml), suggesting that there is a threshold energy requirement below which optimal protein intake is not sufficient to raise the Sm-C. When subjects were refed 18 and 25 kcal/kg, it became apparent that the more energy added to the diet, the greater the absolute concentration of Sm-C attained (0.66 U/ml on 18 kcal/kg and 0.97 U/ml on 25 kcal/kg). Sm-C correlated with nitrogen balance (r = 0.58) during refeeding with the variable energy diets and was a good indicator of acute directional change in nitrogen balance. However, Sm-C was not a reliable indicator of nitrogen repletion, since it rose almost to control levels on the 25 kcal/kg diet while nitrogen balance remained slightly negative.(ABSTRACT TRUNCATED AT 250 WORDS)
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