Protein kinase Ba (PKBa)/AKT1 and PKBß/AKT2 are required for normal peripheral insulin action but their role in pancreatic ß 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, ß cell size and glucose-stimulated insulin secretion in human islets overexpressing either PKBa or PKBß. Our results reveal redundant and specific functions. Overexpression of either isoform resulted in increased ß cell size, but insulin production and secretion remained unchanged. Proliferation and apoptosis of ß cells were only significantly stimulated and inhibited, respectively, by PKBa/AKT1. Importantly, overexpression of PKBa/AKT1 in dissociated islets increased the ratio of ß cells to non-ß cells. These results confirm our previous findings obtained with rodent islets and strongly indicate that PKBa/AKT1 can regulate ß cell mass also in human islets.

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