Journal
CURRENT DIABETES REVIEWS
Volume 6, Issue 1, Pages 52-57Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/157339910790442655
Keywords
Pancreas; Diabetes; alpha-cells; Glucagon; Zinc transporters; Zn (2+)
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Funding
- Novo Nordisk Research Foundation
- Danish Diabetes Association
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Zinc concentrates in islet cells and is related to insulin secretion. Islet cells act as a unit within islets and hormone secretion in the islets is profoundly influenced by paracrine and autocrine regulation. Zinc has been recognised as a candidate paracrine inhibitor of glucagon secretion in alpha-cells. Further zinc fluxes may contribute to regulation of cell mass, Zn2+ may be cytotoxic and Zn2+ depletion by itself can cause cell death induced by oxidative stress. Recently, both free zinc ions and a number of zinc transporters have been localized in alpha-cells. These include zinc importers, ZIP1, ZIP10, and ZIP14 of the SLC39A family and zinc exporters, ZnT1, and ZnT4-8 of the SLC30A family. Furthermore, the redox state of thiol groups and Voltage Gated Ca2+ Channels (VGCC) add to the maintenance of a tight cytoplasmatic zinc homeostasis in the alpha-cells. The ZnT8 protein has emerged as particularly interesting since this zinc transporter has been identified as a genetic risk factor for the development of both type 1 and type 2 diabetes in which both alpha-and beta-cell functions are affected. Recent data discussed here suggest specific effects of Zn2+ on glucagon secretion and other alpha-cell functions.
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