Specific and redundant roles of PKBα/AKT1 and PKBβ/AKT2 in human pancreatic islets

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.