Pancreatic β-Cell Proliferation in Obesity

Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic beta-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in beta-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to beta-cell proliferation. This review focuses on the mechanisms regulating obesity-induced beta-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven beta-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of beta-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study.