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Eva Degerman

Eva Degerman

Professor

Eva Degerman

beta-cell PDE3B regulates Ca(2+)-stimulated exocytosis of insulin.

Author

  • Helena Jones
  • Nils Wierup
  • Jenny Vikman
  • Vincent C Manganiello
  • Eva Degerman
  • Lena Eliasson
  • Lena Stenson

Summary, in English

cAMP signaling is important for the regulation of insulin secretion in pancreatic beta-cells. The level of intracellular cAMP is controlled through its production by adenylyl cyclases and its breakdown by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE3B is involved in the regulation of nutrient-stimulated insulin secretion. Here, aiming at getting deeper functional insights, we have examined the role of PDE3B in the two phases of insulin secretion as well as its localization in the beta-cell. Depolarization-induced insulin secretion was assessed and in models where PDE3B was overexpressed [islets from transgenic RIP-PDE3B/7 mice and adenovirally (AdPDE3B) infected INS-I (832/13) cells], the first phase of insulin secretion, occurring in response to stimulation with high K+ for 5 min, was significantly reduced (similar to 25% compared to controls). In contrast, in islets from PDE3B(-/-) mice the response to high K+ was increased. Further, stimulation of isolated beta-cells from RIP-PDE3B/7 islets, using successive trains of voltage-clamped depolarizations, resulted in reduced Ca2+-triggered first phase exocytotic response as well as reduced granule mobilization-dependent second phase, compared to wild-type beta-cells. Using sub-cellular fractionation, confocal microscopy and transmission electron microscopy of isolated mouse islets and INS-1 (832/13) cells, we show that endogenous and overexpressed PDE3B is localized to insulin granules and plasma membrane. We conclude that PDE3B, through hydrolysis of cAMP in pools regulated by Ca2+, plays a regulatory role in depolarization-induced insulin secretion and that the enzyme is associated with the exocytotic machinery in beta-cells. (c) 2007 Elsevier Inc. All rights reserved.

Department/s

  • Molecular Endocrinology
  • Insulin Signal Transduction
  • Department of Experimental Medical Science
  • Neuroendocrine Cell Biology
  • Diabetes - Islet Cell Exocytosis

Publishing year

2007

Language

English

Pages

1505-1513

Publication/Series

Cellular Signalling

Volume

19

Issue

Feb 12

Document type

Journal article

Publisher

Elsevier

Topic

  • Microbiology

Keywords

  • beta-cell
  • exocytosis
  • insulin
  • cAMP
  • phosphodiesterase 3B

Status

Published

Research group

  • Molecular Endocrinology
  • Insulin Signal Transduction
  • Neuroendocrine Cell Biology
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1873-3913