Topic Overview:
Diabetes occurs when pancreatic beta cells do not secrete enough insulin to meet basic metabolic needs; in both type 1 and type 2 diabetes, the total number of functional beta cells is reduced. A principal goal of diabetes research is to find ways to regenerate lost beta cell mass. In adult mice, the main source of new beta cells is the proliferation of existing beta cells. Alonso’s laboratory hopes to uncover how this proliferation is regulated, so as to discover mechanisms that may represent therapeutic targets to enhance beta cell mass.

It has been known for decades that elevated glucose stimulates beta cell proliferation. In mice, four days of mildly elevated blood glucose results in a five-fold increase in beta cell proliferation. Alonso has developed a new model in which she studies regulators of beta cell proliferation in living mice in response to acute elevation of circulating blood glucose by intravenous infusion.

Using this model, Alonso has shown for the first time that human beta cells proliferate in response to hyperglycemia in vivo, validating both her mouse model as a representation of human biology and her goal of identifying glucose-responsive mitogenic pathways in the beta cell. Alonso is now using this model to explore the regulation of beta cell proliferation in the living pancreas, using genetic and physiological manipulations, and has discovered a novel link between beta cell proliferation and free fatty acids, a crucial nutrient signal that contributes to type 2 diabetes.