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

Barg, Sebastian (author)
Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund
Huang, Ping (author)
University of Chicago, Department of Neurobiology, Pharmacology and Physiology, Chicago
Eliasson, Lena (author)
Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund
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Nelson, Deborah J (author)
University of Chicago, Department of Neurobiology, Pharmacology and Physiology, Chicago
Obermüller, Stefanie (author)
Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund
Rorsman, Patrik (author)
Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund
Thévenod, Frank (author)
Physiologisches Institut, Universität des Saarlandes, Homburg/Saar
Renström, Erik (author)
Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Department of Physiological Sciences, Lund University, Lund
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 (creator_code:org_t)
2001
2001
English.
In: Journal of Cell Science. - 0021-9533 .- 1477-9137. ; 114:Pt 11, s. 2145-54
Related links:
http://jcs.biologist...
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https://lup.lub.lu.s...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

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

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ref (subject category)
art (subject category)

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