Pancreatic Islet Vasculature Adapts to Insulin Resistance Through Dilation and Not Angiogenesis

Pancreatic islets adapt to insulin resistance through a complex set of changes, including b-cell hyperplasia and hypertrophy. To determine if islet vascularization changes in response to insulin resistance, we investigated three independent models of insulin resistance: ob/ob, GLUT4+/2, and mice with high-fat diet–induced obesity. Intravital blood vessel labeling and immunocytochemis-try revealed a vascular plasticity in which islet vessel area was significantly increased, but intraislet vessel density was decreased as the result of insulin resistance. These vascular changes were independent of islet size and were only observed within the b-cell core but not in the islet periphery. Intraislet endothelial cell fen-estration, proliferation, and islet angiogenic factor/receptor ex-pression were unchanged in insulin-resistant compared with control mice, indicating that islet capillary expansion is mediated by dilation of preexisting vessels and not by angiogenesis. W