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.