Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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