Role of beta-cell Toll-like receptor signalling in type 2 diabetes

Diabetes mellitus is a chronic disease that affects over 180 million people worldwide. At least two million Canadians currently live with the condition, a figure expected to double in the next 10 years. Type 2 diabetes accounts for 90 percent of cases and has been recognized by the World Health Organization as a global epidemic. Thus, urgent action is needed to reduce the economic and social burden of the disease and its complications. Diabetes is characterized by insufficient production of insulin, a hormone released by the pancreas that regulates blood glucose levels. Type 1 diabetes is an autoimmune disease caused by destruction of insulin-producing beta-cells within the pancreatic islets. Type 2 diabetes is characterized both by resistance to insulin action and by impaired beta-cell insulin production. Inflammation, an immune response to tissue damage, is important in both conditions. Islets from patients with Type 2 diabetes exhibit increased levels of pro-inflammatory cells and proteins. These contribute to beta-cell damage and impaired insulin production, representing a potential target for therapeutic intervention. High circulating levels of glucose and fatty acids, in addition to toxic deposits of a small protein called islet amyloid polypeptide (IAPP), may signal via pattern recognition receptors on cells within the islet to promote an inflammatory state. However, a better understanding of the causes of islet inflammation is required for effective development of targeted therapies. Clara Westwell-Roper’s research focuses on the role of pattern recognition receptor signalling in islet inflammation induced by metabolic stimuli and IAPP. Her research will enhance our knowledge of the mechanisms that contribute to beta-cell death and impaired insulin secretion in patients with Type 2 diabetes. An understanding of the causes of islet inflammation may facilitate the development of new medications that improve pancreatic islet function.