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ludc web

Lena Eliasson

Principal investigator

ludc web

Novel aspects of the molecular mechanisms controlling insulin secretion

Author

  • Lena Eliasson
  • Fernando Abdulkader
  • Matthias Braun
  • Juris Galvanovskis
  • Michael B. Hoppa
  • Patrik Rorsman

Summary, in English

Pancreatic beta-cells secrete insulin by Ca2+-dependent exocytosis of secretory granules. beta-cell exocytosis involves SNARE (soluble NSF-attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L-type Ca2+ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in beta-cells in intact islets indicate a release rate of similar to 15 granules per beta-cell per second, 100-fold higher than that observed in biochemical assays. Single-vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule lumen with the exterior is similar to 1.4 nm. This is considerably smaller than the size of insulin and membrane fusion is therefore not obligatorily associated with release of the cargo, a feature that may contribute to the different rates of secretion detected by the biochemical and biophysical measurements. However, small molecules like ATP and GABA, which are stored together with insulin in the granules, are small enough to be released via the narrow fusion pore, which accordingly functions as a molecular sieve. We finally consider the possibility that defective fusion pore expansion accounts for the decrease in insulin secretion observed in pathophysiological states including long-term exposure to lipids.

Department/s

  • Diabetes - Islet Cell Exocytosis

Publishing year

2008

Language

English

Pages

3313-3324

Publication/Series

Journal of Physiology

Volume

586

Issue

14

Document type

Journal article review

Publisher

The Physiological Society

Topic

  • Physiology

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1469-7793