Deletion of Ia-2 and/or Ia-2β in mice decreases insulin secretion by reducing the number of dense core vesicles
作者： T. Cai , H. Hirai , G. Zhang , M. Zhang , N. Takahashi
DOI: 10.1007/S00125-011-2221-6
关键词:
摘要: Islet antigen 2 (IA-2) and IA-2β are dense core vesicle (DCV) transmembrane proteins major autoantigens in type 1 diabetes. The present experiments were initiated to test the hypothesis that knockout of genes encoding these impairs secretion insulin by reducing number DCV. Insulin secretion, content DCV evaluated islets from single (Ia-2 [also known as Ptprn] KO, Ia-2β Ptprn2] KO) double (DKO) mice a variety techniques including electron two-photon microscopy, membrane capacitance, Ca2+ currents, half-life, lysosome size autophagy. Islets DKO all showed significant decrease content, half-life (p < 0.05 0.001). Exocytosis capacitance currents supports findings. Electron microscopy KO revealed marked increase 0.001) lysosomes enzymatic studies an cathepsin D activity (p < 0.01). LC3 protein, indicator autophagy, also was increased compared with wild-type 0.01) suggesting autophagy might be involved deletion We conclude resulting Ia-2 and/or Ia-2β, is due
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