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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
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

Abstract 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.

Keywords

  • Endocrinology and Diabetes
  • ClC-3 channels
  • Exocytosis
  • Sulfonylureas
  • Insulin
  • Granular pH

Other

Published
  • Islet cell physiology
  • Islet cell exocytosis
  • Islet patophysiology
  • ISSN: 0021-9533
Erik Renström
E-mail: erik [dot] renstrom [at] med [dot] lu [dot] 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

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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