Polypeptides with nonsuppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization, and some biological properties of forms I and II.
Serum contains a polypeptide with insulin-like activity not suppressible by insulin antibodies (NSILA). A large-scale isolation procedure for NSILA is described, starting from an acid ethanol extract of a Cohn fraction (precipitate B) obtained from human plasma. Two homogenous polypeptides with insulin-like and cell-growth promoting activities could be isolated by gel filtration, ion exchange chromatography, and preparative polyacrylamide gel electrophoresis. Both components are slightly basic polypeptides with a minimal molecular weight of 5800 +/- 400. Both are single-chain molecules with two intrachain disulfide bridges each and no free sulfhydryl groups. NSILA I and II differ, however, in their amino acid compositions. The N-terminal amino acid sequences are Gly-Pro-Glu- in NSILA I, and Ala-Tyr-Arg- and Tyr-Arg- in NSILA II. Both NSILA I and II enhance net gas exchange in adipose tissue with a specific activity 60 times lower than that of insulin. In the range of 1-50 ng/ml, both substances stimulate [3H]thymidine incorporation into DNA of chick embryo fibroblasts. The same effect can be obtained with insulin but only at concentrations 50-100 times higher than those of NSILA. These results suggest that NSILA I and II are two forms of an insulin-like hormone with predominating effects on cell and tissue growth parameters.
D000596:Amino Acids / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D006133:Growth Substances; D006728:Hormones; D006358:Hot Temperature; D006801:Humans; D007328:Insulin; D008970:Molecular Weight; D010455:Peptides
D000596:Amino Acids; D001798:Blood Proteins; D006133:Growth Substances; D006728:Hormones; D007328:Insulin; D010455:Peptides; D004247:DNA