Insulin-Like Growth Factors I and II: Some Biological Actions and Receptor Binding Characteristics of Two Purified Constituents of Nonsuppressible Insulin-Like Activity of Human Serum.

The insulin-like growth factors I and II, two purified constituents of nonsuppressible insulin-like activity of human serum, have been compared with regard to some biological actions in vitro and some receptor-binding characteristics. 1. In the presence of an excess of insulin-antibodies the insulin-like growth factors I and II (a) stimulate the net gas exchange in rat adipose tissue (fat pad assay) to a similar extent; (b) enhance 3-O-methylglucose transport, glucose oxidation and lipogenesis from glucose in rat adipocytes, with slight but significant differences in potency; (c) inhibit lipolysis in adipose tissue from fastedrefed rats, again with slight potency differences. 2. In adipose tissue and adipocytes the biological activity of insulin-like growth factors I and II is between 1⁄35 and 1⁄125 of that of insulin on a molar basis. 3. Insulin-like growth factors I and II are equally potent mitogens (stimulation of DNAsynthesis and cell multiplication in cultured chick embryo fibroblasts). 4. Insulin-like growth factors I and II stimulate 35SO42- incorporation into rat costal cartilage with minor differences in potency. 5. In rat adipocytes, insulin-like growth factors I and II compete with insulin for binding to the insulin receptor. However, their potencies in ‘displacing’ 125I-labeled insulin are between 75 (for factor II) and 290 times (for factor I) lower than that of insulin. In addition, the factors I and II bind to binding sites specific for the factors and for which insulin does not compete. Considerable differences between factors I and II exist regarding their specific binding and their potencies in competing for binding of labeled factors I and IL 6. In chick embryo fibroblasts and isolated chick embryo chondrocytes the insulin-like growth factors I and II compete more or less equally for binding to a binding site specific for the factors and which appears to mediate their effects on cell growth and sulfation. 7. Insulin-like growth factors I and II bind specifically to a partially purified carrier protein of human serum. Pronounced differences in specific binding and in their potencies of competition are observed. Thus, the insulin-like growth factors I and II, two structurally closely related polypeptides, display more or less similar activities in various biological systems in vitro. In all of these, their biological potency can be reasonably correlated with their potency of competition either for the insulin receptor (fat cells) or for a specific binding site (fibroblasts and chondrocytes). In some of the radioactive ligand systems, where the biological function of binding sites for insulin-like growth factor is still unknown (such bindings sites are found in fat cells and on the serum carrier protein), clear cut differences between factors I and II are apparent. [ABSTRACT FROM AUTHOR]

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