Sulfonylurea-Mediated Stimulation of Insulin Exocytosis via an ATP-Sensitive K(+) Channel--Independent Action.

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Abstract

Several reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule pH is necessary for the insulin granule to gain release competence. Proton pumping into the granule is driven by a v-type H(+)-ATPase, but requires simultaneous Cl(-) uptake into the granule via metabolically regulated ClC-3 Cl(-) channels to maintain electroneutrality. Here we discuss the possibility that modulation of granule ClC-3 channels represents the mechanism whereby sulfonylureas directly potentiate the beta-cell exocytotic machinery.

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  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)S33-S36
JournalDiabetes
Volume51
Issue numberSuppl 1
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes