Pten deletion in adult pancreatic beta-cells induces cell proliferation and G1/S cell cycle progression

2013-08-05β-cells, which produce and release insulin play a major role in maintaining glucose homeostasis. PTEN is a lipid phosphatase that antagonizes PI3K/AKT signaling pathway and control cell proliferation, survival, and metabolism. Previous results from our lab indicate that PTEN controls the age onset senescence of β-cells through cyclin D1 dependent p16 signaling pathway. The current study will investigate whether PTEN regulates adult onset β-cell mass and function especially in aging condition, and similar molecular mechanism are involved. ❧ Our lab developed a RIP-CreER⁺, PtenloxP/loxP mouse model in which we are able to induce Pten deletion by tamoxifen treatment on mature mice. I observed evaluated islet mass and functions in mice treated with tamoxifen (Pten null) vs. those treated with vehicle (Pten control), suggesting that maturity onset deletion of Pten leads to significant increase of islet mass and proliferation. In addition, no major difference on fasting and fed glucose or plasma insulin level between Pten null and control mice are observed with minor hyperglycemia conditions observed in juvenile mice, likely due to muscle insulin resistance. I found that proteins regulating G1/S cell cycle transition like those previously observed in PtenL/L; Rip-Cre⁺ mice are similarly altered in mice when PTEN loss is induced in adult stage. The pro-proliferation and anti-aging effects of PTEN in pancreatic β-cells are likely mediated through cyclinD1/Ezh2/p16ink4a signaling pathway