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Loss of a2d-1 calci...
Loss of a2d-1 calcium channel subunit function increases the susceptibility for diabetes
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- Mastrolia, Vincenzo (author)
- Medical University of Innsbruck
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- Flucher, Sylvia M. (author)
- Medical University of Innsbruck
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- Obermair, Gerald J. (author)
- Medical University of Innsbruck
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- Drach, Mathias (author)
- Medical University of Innsbruck
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- Hofer, Helene (author)
- Medical University of Innsbruck
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- Renström, Erik (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Schwartz, Arnold (author)
- University of Cincinnati
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- Striessnig, Jörg (author)
- Medical University of Innsbruck
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- Flucher, Bernhard E. (author)
- Medical University of Innsbruck
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- Tuluc, Petronel (author)
- Medical University of Innsbruck
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(creator_code:org_t)
- 2017-01-23
- 2017
- English 11 s.
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:4, s. 897-907
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http://dx.doi.org/10...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Diabetes
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- By the author/editor
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Mastrolia, Vince ...
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Flucher, Sylvia ...
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Obermair, Gerald ...
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Drach, Mathias
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Hofer, Helene
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Renström, Erik
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show more...
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Schwartz, Arnold
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Striessnig, Jörg
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Flucher, Bernhar ...
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Tuluc, Petronel
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Diabetes
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Lund University