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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification

Author

  • Sebastian Barg
  • P Huang
  • Lena Eliasson
  • D J Nelson
  • Stefanie Obermüller
  • Patrik Rorsman
  • F Thevenod
  • Erik Renström

Summary, in English

ATP-dependent priming of the secretory granules precedes Ca(2+)-regulated neuroendocrine secretion, but the exact nature of this reaction is not fully established in all secretory cell types. We have further investigated this reaction in the insulin-secreting pancreatic B-cell and demonstrate that granular acidification driven by a V-type H(+)-ATPase in the granular membrane is a decisive step in priming. This requires simultaneous Cl(-) uptake through granular ClC-3 Cl(-) channels. Accordingly, granule acidification and priming are inhibited by agents that prevent transgranular Cl(-) fluxes, such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and an antibody against the ClC-3 channels, but accelerated by increases in the intracellular ATP:ADP ratio or addition of hypoglycemic sulfonylureas. We suggest that this might represent an important mechanism for metabolic regulation of Ca(2+)-dependent exocytosis that is also likely to be operational in other secretory cell types.

Department/s

  • Islet cell physiology
  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Islet Patophysiology

Publishing year

2001

Language

English

Pages

2145-2154

Publication/Series

Journal of Cell Science

Volume

114

Issue

Pt 11

Document type

Journal article

Publisher

The Company of Biologists Ltd

Topic

  • Endocrinology and Diabetes

Keywords

  • ClC-3 channels
  • Exocytosis
  • Sulfonylureas
  • Insulin
  • Granular pH

Status

Published

Research group

  • Islet cell physiology
  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 0021-9533