Stimulation of 45Ca uptake and insulin release by 1,1-dimethyl-2-[2-morpholinophenyl] guanidine fumarate in pancreatic islets from Goto-Kakizaki rats

We investigated the effect of the novel oral antidiabetic agent 1,1-dimethyl-2-[2-morpholinophenyl]guanidine fumarate (BTS 67 582) upon Ca-45 net uptake and insulin release in pancreatic islets from diabetic Goto-Kakizaki rats. In the absence of D-glucose, BTS (0.1 mM) augmented Ca-45 uptake, but failed to enhance insulin release significantly. Inversely, in the presence of 8.3 mM D-glucose, BTS (0.1 mM) strikingly increased insulin output, whilst failing to stimulate 45 Ca uptake. These findings indicate that BTS is a suitable agent to augment glucose-induced insulin release in this animal model of non-insulin-dependent diabetes. The secretory response to BTS may involve both the closing of ATP-sensitive K+ channels, with resulting increased influx of Ca2+, and an intracellular redistribution of Ca2+ ions in the islet B-cell.