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    Diabetes. 2007 Mar;56(3):622-33.

    PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.

    Miele C, Raciti GA, Cassese A, Romano C, Giacco F, Oriente F, Paturzo F, Andreozzi F, Zabatta A, Troncone G, Bosch F, Pujol A, Chneiweiss H, Formisano P, Beguinot F.

    Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, via Sergio Pansini 5, Naples 80131, Italy.

    The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. Overexpression of PED/PEA-15 dysregulates beta-cell function and is sufficient to impair glucose tolerance in mice.

    PMID: 17327429 [PubMed - indexed for MEDLINE]

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      Potassium is essential for the proper functioning of the heart, kidneys, muscles, nerves, and digestive system. Usually the food you eat supplies all of the potassium you need. However, certain diseases (e.g., kidney dis...

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