title: Specific and redundant roles of PKBα/AKT1 and PKBβ/AKT2 in human pancreatic islets.
abstract: 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.
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; Competence Center for Personalized Medicine UZH/ETH, Zurich, Switzerland. Electronic address: maren.dietrich@usz.ch.
authors: Maren G
authors: MG
authors: Dietrich
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors: Richard A
authors: RA
authors: Zuellig
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; Competence Center for Personalized Medicine UZH/ETH, Zurich, Switzerland.
authors: Giatgen A
authors: GA
authors: Spinas
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors: Roger
authors: R
authors: Lehmann
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; Competence Center for Personalized Medicine UZH/ETH, Zurich, Switzerland.
authors: Oliver
authors: O
authors: Tschopp
authors: Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; Competence Center for Personalized Medicine UZH/ETH, Zurich, Switzerland.
authors: Markus
authors: M
authors: Niessen
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*
chemical_list: D007328:Insulin; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Insulin secretion; Islets of Langerhans; Protein kinase B; β cell mass