Differential mechanisms of glucose and palmitate in augmentation of insulin secretion in mouse pancreatic islets.

Abstract

To assess the possible importance of saturated fatty acids in glucose amplification of K+ATP channel-independent insulin secretion. Insulin release from perifused pancreatic islets of NMRI mice was determined by radioimmunoassay. In the presence of K+ (20 mmol/l) and diazoxide (250 micromol/l), which stimulates Ca2+ influx and opens K+ATP channels, palmitate (165 micromol/l total; 1.2 micromol/l free) increased insulin secretion at 3.3, 10 and 16.7 mmol/l glucose while glucose (10; 16.7 mmol/l) did not increase insulin secretion. In the presence of K+ (60 mmol/l) and diazoxide (250 micromol/l), glucose (10; 16.7 mmol/l) stimulation of K+ATP channel-independent insulin secretion increased, whereas the effectiveness of palmitate (165 micromol/l total; 1.2 micromol/l free) on insulin secretion at both 3.3, 10 or 16.7 mmol/l glucose was reduced. Palmitate thereby mimicked the stimulatory pattern of the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (0.16 micromol/l), which also failed to increase insulin secretion at maximum depolarising concentrations of K+ (60 mmol/l). Furthermore, the protein kinase C inhibitor calphostin C (1 micromol/1), led to a complete suppression of the effects of both palmitate (165 micromol/l total; 1.2 micromol/l free) and myristate (165 micromol/l total; 2.4 micromol/l free) stimulation of glucose (16.7 mmol/l)-induced insulin secretion. Calphostin C (1 micromol/l), however, failed to affect insulin secretion induced by glucose (16.7 mmol/l). These data suggest that glucose could increase insulin secretion independently of saturated fatty acids like palmitate and myristate, which amplify glucose-induced insulin secretion by activation of protein kinase C.