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.

ludc web

Lena Eliasson

Principal investigator

ludc web

Multivesicular exocytosis in rat pancreatic beta cells

Author

  • M. B. Hoppa
  • E. Jones
  • J. Karanauskaite
  • R. Ramracheya
  • M. Braun
  • S. C. Collins
  • Q. Zhang
  • A. Clark
  • Lena Eliasson
  • C. Genoud
  • P. E. MacDonald
  • A. G. Monteith
  • S. Barg
  • J. Galvanovskis
  • P. Rorsman

Summary, in English

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.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes - Islet Cell Exocytosis

Publishing year

2012

Language

English

Pages

1001-1012

Publication/Series

Diabetologia

Volume

55

Issue

4

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Exocytosis
  • Ca2+
  • Beta cell

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1432-0428