
Erik Renström
Vice-chancellor

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