Mechanistic insights into pancreatic beta-cell mass regulation by glucose and free fatty acids

Pancreatic islets are responsible for blood glucose homeostasis. Reduced numbers of functional (insulin-secreting) beta-cells in pancreatic islets underlies diabetes. Restoration of the secretion of the proper amount of insulin is a goal. Beta-cell mass is increased by neogenesis, proliferation and cell hypertrophy, and is decreased by beta-cell death primarily through apoptosis. Many hormones and nutrients affect beta-cell mass, and glucose and free fatty acid are thought to be the most important determinants of beta-cell equilibrium. A number of molecular pathways have been implicated in beta-cell mass regulation and have been studied. This review will focus on the role of the principle metabolites, glucose and free fatty acid, and the downstream signaling pathways regulating beta-cell mass by these metabolites.