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

• Published in: Experimental cell research 2015-10, Vol.338 (1), p.82-88
• Main Authors: Dietrich, Maren G., Zuellig, Richard A., Spinas, Giatgen A., Lehmann, Roger, Tschopp, Oliver, Niessen, Markus
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; APOPTOSIS; CARBOXYLIC ACIDS; CELL PROLIFERATION; Cell Size; Cells, Cultured; COMPLEXES; DEOXYURIDINE; GLUCOSE; HEMAGGLUTININS; HUMAN POPULATIONS; Humans; INSULIN; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - enzymology; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - physiology; Islets of Langerhans; KNOCK-OUT REACTIONS; LYMPHOKINES; MICE; PANCREAS; PHENOTYPE; PHOSPHOTRANSFERASES; Protein kinase B; Proto-Oncogene Proteins c-akt - physiology; RATS; RECEPTORS; REGULATIONS; SECRETION; SUBSTRATES; β cell mass
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2015.08.008

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. •PKBα and PKBβ have specific but also redundant functions in human pancreatic islets.•Only PKBα drives islet and β cell proliferation.•Only PKBα protects β cells and islets from apoptosis.•Both isoforms can increase β cell size.•Regulation of islet mass seems to be conserved between rodent and human.