Effects of a Synthetic Hexapeptide (β-Ala-Arg-Gly-Phe-Phe-Tyr-NH₂) on Insulin Binding and Glucose Metabolism of Rat Adipocytes

Abstract

A stimulatory action of DP-432, a modified insulin B-chain fragment (B_21-26), on glucose metabolism of rat adipocytes was studied in vitro.

DP-432 (≥ 5 mM) stimulated glucose oxidation of adipocytes, but did not inhibit ¹²⁵I-insulin binding to the cells. The stimulatory action of the peptide was inhibited by enzymatic digestion of the cells with neuraminidase but not by the treatment with trypsin. Neither was enzymatic treatment of the cells inhibitory to the action of insulin.

Cytochalasin B, an inhibitor of hexose transport, completely diminished the stimulatory action of DP-432 on glucose oxidation at 0.2, 1, and 10 mM medium glucose concentrations. The action of insulin was also completely depressed by the inhibitor at 0.2 mM glucose, but was recovered by increasing glucose concentration from 1 to 10 mM. Furthermore, DP-432 had no effect on oxidation of fructose which entered the cells independently of insulin-dependent hexose transport system.

Insulin-stimulated glucose oxidation was further increased by addition of 0.1 mM DP-432 to the medium, which alone had no effect on the metabolism. Such an effect of the peptide was observed with concanavalin A-stimulated but not with ouabain-stimulated glucose oxidation.

From these results, DP-432 appears to stimulate glucose oxidation without binding to insulin receptors on the cell surface. The peptide is different from insulin in that it does not stimulate intracellular metabolism of sugar directly. Furthermore, the peptide is likely to exaggerate or potentiate enhancing actions of insulin or concanavalin A on glucose metabolism which come from occupation of components on the cell surface by these proteins.

Key words

Insulin β-chain Fragment B 21-26 - Rat Adipocytes - Insulin-Like Activity - Insulin-Potentiating Activity - Insulin Action - Insulin Receptor - Glucose Transport - Glucose Oxidation - Fructose Oxidation - Intracellular Hexose Metabolism