| First Author | Wang L | Year | 2010 |
| Journal | Diabetes | Volume | 59 |
| Issue | 12 | Pages | 3117-26 |
| PubMed ID | 20852026 | Mgi Jnum | J:170206 |
| Mgi Id | MGI:4944141 | Doi | 10.2337/db09-1805 |
| Citation | Wang L, et al. (2010) Deletion of Pten in pancreatic ss-cells protects against deficient ss-cell mass and function in mouse models of type 2 diabetes. Diabetes 59(12):3117-26 |
| abstractText | OBJECTIVE: Type 2 diabetes is characterized by diminished pancreatic beta-cell mass and function. Insulin signaling within the beta-cells has been shown to play a critical role in maintaining the essential function of the beta-cells. Under basal conditions, enhanced insulin-PI3K signaling via deletion of phosphatase with tensin homology (PTEN), a negative regulator of this pathway, leads to increased beta-cell mass and function. In this study, we investigated the effects of prolonged beta-cell-specific PTEN deletion 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 beta-cell-specific PTEN deletion (RIPcre(+) Pten(fl/fl)). RESULTS: PTEN expression in islets was upregulated in both models of type 2 diabetes. RIPcre(+) Pten(fl/fl) mice were completely protected against diabetes in both models of type 2 diabetes. The islets of RIPcre(+) Pten(fl/fl) mice already exhibited increased beta-cell mass under basal conditions, and there was no further increase under diabetic conditions. Their beta-cell function and islet PI3K signaling remained intact, in contrast to HFD-fed wild-type and db/db islets that exhibited diminished beta-cell function and attenuated PI3K signaling. These protective effects in beta-cells occurred in the absence of compromised response to DNA-damaging stimuli. CONCLUSIONS: PTEN exerts a critical negative effect on both beta-cell mass and function. Thus PTEN inhibition in beta-cells can be a novel therapeutic intervention to prevent the decline of beta-cell mass and function in type 2 diabetes. |
