Zinc, alpha cells and glucagon secretion.
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.
Egefjord
Laerke
L
Department of Pharmacology, University of Aarhus, Aarhus, Denmark. le@studmed.au.dk
Petersen
Andreas B
AB
Rungby
Jørgen
J
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D027682:Cation Transport Proteins; D015221:Potassium Channels; C403517:SLC39A1 protein, human; C519886:SLC39A10 protein, human; C497524:SLC39A14 protein, human; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005934:Glucagon; D015032:Zinc