title: D-chiro-inositol glycan stimulates insulin secretion in pancreatic β cells.
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.
authors: Department of Pharmacology, University of Virginia Health System, Charlottesville, VA, United States.
authors: Roman
authors: R
authors: Lazarenko
authors: Department of Pharmacology, University of Virginia Health System, Charlottesville, VA, United States.
authors: Jessica
authors: J
authors: Geisler
authors: Department of Pharmacology, University of Virginia Health System, Charlottesville, VA, United States.
authors: Douglas
authors: D
authors: Bayliss
authors: Department of Pharmacology, University of Virginia Health System, Charlottesville, VA, United States.
authors: Joseph
authors: J
authors: Larner
authors: Department of Pharmacology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: cl4xd@virginia.edu.
authors: Chien
authors: C
authors: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D004187:Disaccharides / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology; D000071636:Protein Phosphatase 2C; D034622:RNA Interference; D034741:RNA, Small Interfering; D064233:Sulfonylurea Receptors / Q000819:agonists; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: C476439:4-(2-amino-2-deoxygalactopyranosyl)-3-O-methylinositol; D004187:Disaccharides; D007004:Hypoglycemic Agents; D007295:Inositol Phosphates; D007328:Insulin; D054086:KATP Channels; D011134:Polysaccharides; D034741:RNA, Small Interfering; D064233:Sulfonylurea Receptors; C028039:inositol phosphate glycan; D014044:Tolbutamide; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C
keywords: INS-2; Insulin secretion; Islet; K(ATP); MIN6; PP2C