D-chiro-inositol glycan stimulates insulin secretion in pancreatic β cells

Insulin has been shown to act on pancreatic beta cells to regulate its own secretion. Currently the mechanism underlying this effect is unclear. INS-2, a novel inositol glycan pseudo-disaccharide containing D-chiro-inositol and galactosamine, has been shown to function as an insulin mimetic and a putative insulin mediator. In the present study we found that INS-2 stimulates insulin secretion in MIN6 beta cells and potentiates glucose stimulated insulin secretion in isolated mouse islets. Importantly, INS-2 failed to potentiate insulin secretion induced by tolbutamide, which stimulates insulin release by closing ATP sensitive potassium channels (K-ATP). Electrophysiological studies showed that INS-2 inhibited sulfonylurea-sensitive K-ATP conductance. The effect of INS-2 on inhibiting K-ATP channel is mediated by protein phosphatase 2C (PP2C), as knocking down PP2C expression in MIN6 cells by PP2C small hairpin RNA completely abolished the effect of INS-2 on K-ATP, and consequently attenuated INS-2 induced insulin secretion. In conclusion, the present study identifies a novel mechanism involving PP2C in regulating K-ATP channel activity and consequently insulin secretion. (C) 2014 Elsevier Ireland Ltd. All rights reserved.