Project 172623

Many people with type 2 diabetes must take insulin by injection because of the loss of insulin-producing cells, called islet beta cells, in their pancreas. It is thought that this loss of islet beta cells is due islet amyloid, a toxic accumulation of protein. In order to better understand why protein builds up in people with type 2 diabetes, we propose to study the forms of a protein hormone called pro-islet amyloid polypeptide (proIAPP). ProIAPP is made within the insulin-producing islet beta cells. When it is cut by enzymes, it becomes a smaller protein hormone called islet amyloid polypeptide (IAPP). Islet amyloid forms when, for unknown reasons, IAPP forms aggregates that kill the islet beta cells. We believe that in type 2 diabetes, the process through which proIAPP is cut to form IAPP is defective, leading to an accumulation of incompletely cut forms of proIAPP, that then aggregate to form amyloid. We will study the forms of proIAPP in the blood of persons with type 2 diabetes and in mice that make excessive amounts of the protein hormone. Through this research, we hope to understand why islet amyloid occurs in people with type 2 diabetes. Our goal is to contribute to developing new therapies that may prevent this protein buildup and the resulting destruction of the pancreas' insulin producing cells.