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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

CAPS1 and CAPS2 Regulate Stability and Recruitment of Insulin Granules in Mouse Pancreatic beta Cells.

Author

  • Dina Speidel
  • S Albert Salehi
  • Stefanie Obermueller
  • Ingmar Lundquist
  • Nils Brose
  • Erik Renström
  • Patrik Rorsman

Summary, in English

CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability.

Department/s

  • Diabetes - Islet Patophysiology
  • Diabetes - Islet Cell Exocytosis
  • Islet cell physiology

Publishing year

2008

Language

English

Pages

57-67

Publication/Series

Cell Metabolism

Volume

7

Issue

1

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Diabetes - Islet Cell Exocytosis
  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1550-4131