Grant: Operating Grant

Diabetes affects 2 million Canadians and costs our healthcare system nearly $15 billion dollars annually in direct and indirect costs. An inability of pancreatic islet of Langerhans to secrete sufficient amounts of insulin is central to the development and progression of type 2 diabetes, which accounts for more than 80% of cases. It is therefore essential that we gain a further understanding of the mechanisms and processes regulating insulin secretion in order to: 1) understand potential defects that occur in type 2 diabetes; and 2) develop improved strategies for the treatment, prevention and ultimate cure of the disease. In the present study we will examine the role of a novel signalling pathway, known as SUMOylation, in the acute regulation of insulin secretion from islet beta-cells. Recent work from us and others suggests that this pathway, thought to function primarily in gene transcription, may be an important regulator of cellular electrical activity. New data from our lab also supports a role for SUMOylation in controlling the cellular machinery responsible for the actual release of insulin (the 'exocytotic' machinery). Thus, we hypothesize that SUMOylation represents an important new pathway for the regulation of insulin secretion. We will therefore examine the role of this pathway in regulating the cellular function of mouse and human insulin-secreting pancreatic beta-cells in health and in models of diabetes.