title: Pancreatic beta cell mass preserved in heterozygous PDK1 knockout mice.
abstract: We have demonstrated that 3-phosphoinositide-dependent protein kinase 1 (PDK1) contributes to signaling by insulin or insulin-like growth factor-1 (IGF-1) that is responsible for the regulation of both the number and size of pancreatic beta cells in mice. Complete ablation of PDK1 in pancreatic beta cells leads to progressive hyperglycemia as a result of loss of beta cell mass. In this study, we generated heterozygous pancreatic beta cell-specific PDK1 knockout (betaPDK1+/-) mice and fed them a high-fat diet as a model of human type 2 diabetes. The betaPDK1+/- mice exhibited normal glucose tolerance even on a high-fat diet. Further, islet morphology and beta cell mass were normal in betaPDK1+/- mice, and haploinsufficiency of PDK1 did not impair the compensatory hyperplasia of beta cells on a high-fat diet. The phosphorylation and expression of the molecules that are expressed downstream of PDK1 were similar in the islets of the betaPDK1+/- and control mice. Eventually, we concluded that glucose homeostasis and islet mass were maintained in betaPDK1+/- mice.
authors.affiliation: Department of Internal Medicine, Division of Diabetes, Metabolism, and Endocrinology, Kobe University Graduate School of Medicine, Kobe 17, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kido
authors.forename: Naoko
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D048429:Cell Size; D006579:Heterozygote; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D007328:Insulin; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; C578564:Pdpk1 protein, mouse; D017346:Protein Serine-Threonine Kinases