Abstract

Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also impacts pancreatic β cells. To directly examine the alterations that occur in islet morphology, as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from non-diabetic subjects who were either insulin resistant or insulin sensitive. We also compared insulin sensitivity, insulin secretion and incretin levels between the two groups. We report an increased islet size, and an elevated number of both β and α cells that resulted in an altered β:α cell area in the insulin resistant group. Our data suggest that neogenesis from duct cells and transdifferentiation of α cells are potential contributors to the β cell compensatory response to insulin resistance in the absence of overt diabetes.