Effect of insulin fragments on biological activity of insulin and desoctapeptide insulin. I. Potentiation of biological activities.

Four derivatives of the insuln B-chain COOH-terminal pentapeptide Arg-Gly-Phe-Phe-Tyr (B22-26) were synthesized and shown to be inactive alone. In the presence of submaximal concentrations of insulin or desoctapeptide insulin, peptides at concentrations of 10(-4) M and higher, markedly stimulated the actions of insulin on rat adipocytes including labeled glucose oxidation, activation of glycogen synthase, and stimulation of 2-deoxyglucose transport. The B-chain COOH-terminal heptapeptide, Gly-Phe-Phe-Tyr-Thr-Pro-Lys (B23-29) was inactive alone or in the presence of submaximal concentrations of insulin or desoctapeptide insulin, suggesting that argnine is required. Dose response curves of insulin, and desoctapeptide insulin for labeled glucose oxidation by rat adipocytes were shifted 1 log concentration unit to the left in the presence of peptide. Peptide shortened the lag time of labeled glucose oxidation and markedly enhanced the rate of 14CO2 production following the lag time. Peptides also enhanced insulin-like activities of concanavalin A and nonsuppressible insulin-like activity P.