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.

ChemInform Abstract: The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo‐Inositol Chemistry)

“…[155] INS-2s timulatesinsulin secretioninMIN6 b cells, andpotentiatesglucosestimulated insulinsecretion in isolated mouseislets. [156] It does this throughamechanismthatinvolvest he stimulationofthe…”

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…[155] In MIN6 β cells INS-2 stimulates insulin secretion and in isolated mouse islets it potentiates glucose stimulated insulin secretion. [156] It does this through a mechanism that involves the stimulation of the protein phosphatase 2C mediated inhibition of ATP sensitive potassium channels.…”

Die “anderen” Inositole und ihre Phosphate: Synthese, Biologie und Medizin (sowie jüngste Fortschritte in dermyo‐Inositolchemie)

“…[155] In MIN6-b-Zellen stimuliert INS-2 die Insulinsekretion und verstärkt in isolierten Maus-Inseln die Glucose-stimulierte Insulinsekretion. [156] Daran wirkt die Stimulation der Proteinphosphatase-2C-vermittelten Hemmung von ATPempfindlichen Kaliumkanälen mit.…”