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Multivesicular exoc...
Multivesicular exocytosis in rat pancreatic beta cells
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Hoppa, M. B. (author)
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Jones, E. (author)
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Karanauskaite, J. (author)
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Ramracheya, R. (author)
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Braun, M. (author)
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Collins, S. C. (author)
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Zhang, Q. (author)
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Clark, A. (author)
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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Genoud, C. (author)
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MacDonald, P. E. (author)
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Monteith, A. G. (author)
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- Barg, Sebastian (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Barg
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Galvanovskis, J. (author)
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Rorsman, P. (author)
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(creator_code:org_t)
- 2011-12-22
- 2012
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:4, s. 1001-1012
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Abstract
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- To establish the occurrence, modulation and functional significance of compound exocytosis in insulin-secreting beta cells. Exocytosis was monitored in rat beta cells by electrophysiological, biochemical and optical methods. The functional assays were complemented by three-dimensional reconstruction of confocal imaging, transmission and block face scanning electron microscopy to obtain ultrastructural evidence of compound exocytosis. Compound exocytosis contributed marginally (< 5% of events) to exocytosis elicited by glucose/membrane depolarisation alone. However, in beta cells stimulated by a combination of glucose and the muscarinic agonist carbachol, 15-20% of the release events were due to multivesicular exocytosis, but the frequency of exocytosis was not affected. The optical measurements suggest that carbachol should stimulate insulin secretion by similar to 40%, similar to the observed enhancement of glucose-induced insulin secretion. The effects of carbachol were mimicked by elevating [Ca2+](i) from 0.2 to 2 mu mol/l Ca2+. Two-photon sulforhodamine imaging revealed exocytotic events about fivefold larger than single vesicles and that these structures, once formed, could persist for tens of seconds. Cells exposed to carbachol for 30 s contained long (1-2 mu m) serpentine-like membrane structures adjacent to the plasma membrane. Three-dimensional electron microscopy confirmed the existence of fused multigranular aggregates within the beta cell, the frequency of which increased about fourfold in response to stimulation with carbachol. Although contributing marginally to glucose-induced insulin secretion, compound exocytosis becomes quantitatively significant under conditions associated with global elevation of cytoplasmic calcium. These findings suggest that compound exocytosis is a major contributor to the augmentation of glucose-induced insulin secretion by muscarinic receptor activation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Exocytosis
- Ca2
- Beta cell
- Beta cell
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Hoppa, M. B.
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Jones, E.
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Karanauskaite, J ...
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Ramracheya, R.
-
Braun, M.
-
Collins, S. C.
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show more...
-
Zhang, Q.
-
Clark, A.
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Eliasson, Lena
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Genoud, C.
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MacDonald, P. E.
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Monteith, A. G.
-
Barg, Sebastian
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Galvanovskis, J.
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Rorsman, P.
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Diabetologia
- By the university
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Lund University
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Uppsala University