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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

Loss of a2d-1 calcium channel subunit function increases the susceptibility for diabetes

Author

  • Vincenzo Mastrolia
  • Sylvia M. Flucher
  • Gerald J. Obermair
  • Mathias Drach
  • Helene Hofer
  • Erik Renström
  • Arnold Schwartz
  • Jörg Striessnig
  • Bernhard E. Flucher
  • Petronel Tuluc

Summary, in English

Reduced pancreatic b-cell function or mass is the critical problem in developing diabetes. Insulin release from b-cells depends on Ca2+ influx through high voltage- gated Ca2+ channels (HVCCs). Ca2+ influx also regulates insulin synthesis and insulin granule priming and contributes to β-cell electrical activity. The HVCCs aremultisubunit protein complexes composed of a pore-forming a1 and auxiliary β and α2δ subunits. α2δ is a key regulator of membrane incorporation and function of HVCCs. Here we show that genetic deletion of α2δ-1, the dominant α 2δ subunit in pancreatic islets, results in glucose intolerance and diabetes without affecting insulin sensitivity. Lack of the α 2δ-1 subunit reduces the Ca2+ currents through all HVCC isoforms expressed in b-cells equally in male and female mice. The reduced Ca2+ influx alters the kinetics and amplitude of the global Ca2+ response to glucose in pancreatic islets and significantly reduces insulin release in both sexes. The progression of diabetes in males is aggravated by a selective loss of b-cell mass, while a stronger basal insulin release alleviates the diabetes symptoms in most α2δ -1 2/2 female mice. Together, these findings demonstrate that the loss of the Ca2+ channel α2β-1 subunit function increases the susceptibility for developing diabetes in a sex-dependent manner.

Department/s

  • Diabetes - Islet Patophysiology
  • Department of Clinical Sciences, Malmö
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2017-04-01

Language

English

Pages

897-907

Publication/Series

Diabetes

Volume

66

Issue

4

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 0012-1797