Amanda Ackermann's Research
THE ROLE OF FOXM1 IN BETA CELL MASS EXPANSION AND REGENERATION
I am interested in how an organism maintains its beta cell mass at appropriate levels throughout its lifetime in order to maintain glucose homeostasis. Beta cell mass can increase in normal individuals in response to obesity or pancreatic injury, by increasing beta cell proliferation, beta cell neogenesis, and/or beta cell size. However, one or more of these processes does not occur properly in Type II diabetic patients. Thus, identifying factors that play a role in each of these processes could lend insight into why diabetes may occur and how it could possibly be treated. I am studying the role that the FoxM1 transcription factor may play in these processes, by comparing beta cell responses after pancreatic injury and diet-induced obesity between wild-type and pancreas-wide FoxM1 knockout mice (KO). These mice at baseline exhibit reduced beta cell proliferation, reduced islet size, and increased beta cell size versus wildtype littermates. When fed a high-fat/high-carbohydrate diet, the KO mice are more susceptible to developing glucose intolerance and diabetes than are their wild-type littermates. These KO mice are also unable to properly regenerate their beta cell mass following surgical removal of a portion of their pancreas. Because the process of beta cell mass regeneration is thought to recapitulate the development of beta cell mass that occurs during embryogenesis, I am now investigating FoxM1's role in the embryonic pancreas. We are interested in determining whether FoxM1 is necessary only for beta cell proliferation, or whether it also plays a role in beta cell differentiation and function.