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

Barg, SebastianLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund (author)

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.

Huang, PingUniversity of Chicago, Department of Neurobiology, Pharmacology and Physiology, Chicago (author)
Eliasson, LenaLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund(Swepub:lu)mphy-lel (author)
Nelson, Deborah JUniversity of Chicago, Department of Neurobiology, Pharmacology and Physiology, Chicago (author)
Obermüller, StefanieLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund(Swepub:lu)mphy-sob (author)
Rorsman, PatrikLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund(Swepub:lu)mphy-pro (author)
Thévenod, FrankPhysiologisches Institut, Universität des Saarlandes, Homburg/Saar (author)
Renström, ErikLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund(Swepub:lu)mphy-ere (author)
Islet cell physiologyForskargrupper vid Lunds universitet (creator_code:org_t)

By the author/editor: Barg, Sebastian; Huang, Ping; Eliasson, Lena; Nelson, Deborah ...; Obermüller, Stef ...; Rorsman, Patrik; show more...; Thévenod, Frank; Renström, Erik; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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