Stimulation of insulin secretion by noncarbohydrate metabolites.

Abstract

Insulin secretion in incubated pieces of rat pancreatic tissue is stimulated by phydroxybutyrate, palmitate, possibly lecithin, but not by octanoate. Leucine, arginine, tryptophane, phenylalanine, lysine, and glycine also stimulate insulin secretion. Stimulation by the lipid and protein metabolites is observed at low glucose concentrations, in the absence of glucose, or in the simultaneous presence of glucose in high concentration and mannoheptulose, but it cannot be detected when glucose alone is present in high concentration. The stimulant effects upon insulin secretion of these noncarbohydrate metabolites are compared with those of glucose, tolbutamide, and theophylline. This comparison suggests that the lipid and protein metabolites stimulate insulin secretion in a process comparable to that induced by glucose itself, and that the range of glucose concentrations in which they are effective depends upon thoir ability to mimic the effect, of this sugar. These findings also suggest that oxidation of substrates through the Krebs cycle could provide both the signal and energy required for the process of insulin secretion and that keto-acids, fatty acids, and amino acids might be involved in a feedback control mechanism of insulin secretion in vivo, comparable to that existing for glucose. R ecent reports have revealed that insulin secretion is stimulated by noncarbohydrate metabolites such as amino acids1 keto-acids2 and fatty acids.3 In these recent studies, the stimulant effect of noncarbohydrate metabolites upon insulin secretion was investigated in vivo, under conditions of normogIycemia in the postabsorptive state. This procedure does not allow measurement of any direct effect of the administered substances upon the beta cells and does not afford any information concerning the effects of these substances at various