Deletion of Pten in Pancreatic -Cells Protects Against Deficient -Cell Mass and Function in Mouse Models of

OBJECTIVE—Type 2 diabetes is characterized by diminished pancreatic -cell mass and function. Insulin signaling within the -cells has been shown to play a critical role in maintaining the essential function of the -cells. Under basal conditions, en-hanced insulin-PI3K signaling via deletion of phosphatase with tensin homology (PTEN), a negative regulator of this pathway, leads to increased -cell mass and function. In this study, we investigated the effects of prolonged -cell–specific PTEN dele-tion in models of type 2 diabetes. RESEARCH DESIGN AND METHODS—Two models of type 2 diabetes were employed: a high-fat diet (HFD) model and a db/db model that harbors a global leptin-signaling defect. A Cre-loxP system driven by the rat insulin promoter (RIP) was employed to obtain mice with -cell–specific PTEN deletion (RIPcre Ptenfl/fl)