Referenced in: none

Automatically associated channels: Kir2.3

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

Authors: Roman Lazarenko, Jessica Geisler, Douglas Bayliss, Joseph Larner, Chien Li

Journal, date & volume: Mol. Cell. Endocrinol., 2014 Apr 25 , 387, 1-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24530497

Abstract
Insulin has been shown to act on pancreatic β 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 β 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 (KATP). Electrophysiological studies showed that INS-2 inhibited sulfonylurea-sensitive KATP conductance. The effect of INS-2 on inhibiting KATP 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 KATP and consequently attenuated INS-2 induced insulin secretion. In conclusion, the present study identifies a novel mechanism involving PP2C in regulating KATP channel activity and consequently insulin secretion.