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

Author:
  • Erik Renström
  • Sebastian Barg
  • Frank Thévenod
  • Patrik Rorsman
Publishing year: 2002
Language: English
Pages: 33-36
Publication/Series: Diabetes
Volume: 51
Issue: Suppl 1
Document type: Journal article
Publisher: American Diabetes Association

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Islet patophysiology
  • Islet cell physiology
  • ISSN: 1939-327X
Erik Renström
E-mail: erik.renstrom [at] med.lu.se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00