Project summary/Abstract Type 2 diabetes is a major health concern in the United States. It occurs when individuals fail to compensate for an increased demand for insulin from the pancreatic β cells. The prostaglandin E receptor EP3 (encoded by Ptger3), which responds to prostaglandin E2 (PGE2), has been shown to inhibit insulin secretion. EP3 is upregulated in diabetic individuals and with age. Data from our lab has demonstrated that ex vivo pharmacological inhibition of EP3 increases β cell mass and survival. The role of EP3 specifically in the β cell has not been examined. I propose using a β-cell-specific EP3 KO mouse model to determine the effect of EP3 inactivation in the context of high fat diet. In addition, FoxM1 is a transcription factor necessary for β cell proliferation. FoxM1 levels decrease with age while EP3 levels increase. In this proposal, I outline experiments to elucidate what role, if any, FoxM1 has in regulating Ptger3 expression.