Dietrich Maren G, Zuellig Richard A, Spinas Giatgen A, Lehmann Roger, Tschopp Oliver, Niessen Markus
Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; Competence Center for Personalized Medicine UZH/ETH, Zurich, Switzerland.
Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
Exp Cell Res. 2015 Oct 15;338(1):82-8. doi: 10.1016/j.yexcr.2015.08.008. Epub 2015 Aug 28.
Protein kinase Bα (PKBα)/AKT1 and PKBβ/AKT2 are required for normal peripheral insulin action but their role in pancreatic β cells remains enigmatic as indicated by the relatively mild islet phenotype of mice with deficiency for either one of these two isoforms. In this study we have analysed proliferation, apoptosis, β cell size and glucose-stimulated insulin secretion in human islets overexpressing either PKBα or PKBβ. Our results reveal redundant and specific functions. Overexpression of either isoform resulted in increased β cell size, but insulin production and secretion remained unchanged. Proliferation and apoptosis of β cells were only significantly stimulated and inhibited, respectively, by PKBα/AKT1. Importantly, overexpression of PKBα/AKT1 in dissociated islets increased the ratio of β cells to non-β cells. These results confirm our previous findings obtained with rodent islets and strongly indicate that PKBα/AKT1 can regulate β cell mass also in human islets.
蛋白激酶Bα（PKBα）/AKT1和蛋白激酶Bβ（PKBβ）/AKT2是正常外周胰岛素作用所必需的，但正如缺乏这两种亚型之一的小鼠相对较轻的胰岛表型所示，它们在胰腺β细胞中的作用仍然不明。在本研究中，我们分析了过表达PKBα或PKBβ的人胰岛中的增殖、凋亡、β细胞大小和葡萄糖刺激的胰岛素分泌。我们的结果揭示了冗余和特定的功能。任一亚型的过表达均导致β细胞大小增加，但胰岛素产生和分泌保持不变。β细胞的增殖和凋亡分别仅被PKBα/AKT1显著刺激和抑制。重要的是，在解离的胰岛中过表达PKBα/AKT1增加了β细胞与非β细胞的比例。这些结果证实了我们之前在啮齿动物胰岛中获得的发现，并有力地表明PKBα/AKT1也可以调节人胰岛中的β细胞质量。
