Selective deletion of Pten in pancreatic β cells leads to increased islet mass and resistance to STZ-induced diabetes

被引:111
作者
Stiles, BL [1 ]
Kuralwalla-Martinez, C
Guo, W
Gregorian, C
Wang, Y
Tian, JD
Magnuson, MA
Wu, H
机构
[1] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA
[2] Childrens Hosp Orange Cty, Div Neonatol, Dept Pediat, Orange, CA 92668 USA
[3] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN USA
关键词
D O I
10.1128/MCB.26.7.2772-2781.2006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. In this study, we deleted Pten specifically in the insulin producing beta cells during murine pancreatic development. Pten deletion leads to increased cell proliferation and decreased cell death, without significant alteration of beta-cell differentiation. Consequently, the mutant pancreas generates more and larger islets, with a significant increase in total beta-cell mass. PTEN loss also protects animals from developing streptozotocin-induced diabetes. Our data demonstrate that PTEN loss in beta cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for beta-cell protection and regeneration therapies.
引用
收藏
页码:2772 / 2781
页数:10
相关论文
共 57 条