Grant: Operating Grant

Patients with type 2 diabetes are unable to produce sufficient insulin to meet demand and blood sugars rise as a result. The disease worsens as insulin-producing beta cells in the pancreas lose their function and die. Loss of beta cells is thought to be due to several causes, one being the formation of toxic protein aggregates called islet amyloid, formed by accumulations of another small protein made along with insulin, called islet amyloid polypeptide (IAPP). In type 2 diabetes the islets in the pancreas, where the insulin-producing beta cells reside, also show signs of inflammation. We recently found that aggregates of IAPP - the toxic amyloid deposits - may play an important role in inducing this inflammation within the islet. In this proposal we try to understand the mechanism by which IAPP aggregates induce islet inflammation in diabetes, and evaluate therapeutic approaches to block amyloid-induced inflammation. Findings from these studies may aid in the development of strategies to preserve beta cells in persons with type 2 diabetes.