Effect of cholesterol on prohormone processing in pancreatic beta cells in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is a devastating chronic disease affecting close to two million Canadians. The disease is characterized by a loss of insulin action in tissues such as muscle and a loss of insulin secretion by the islet beta cells of the pancreas. The number of beta cells within the pancreas – an important determinant of the amount of insulin secreted – is decreased in persons with type 2 diabetes. This supports the idea that the progressive loss of insulin secretion in this disease is due to a loss of functional beta cells. The loss of beta cells is associated with the formation of toxic islet amyloid deposits, consisting primarily of the beta cell peptide islet amyloid polypeptide (IAPP or amylin). Although the mechanism underlying islet amyloid formation is not known, impaired processing of the IAPP precursor, proIAPP, has been proposed to be an important initiating event. In type 2 diabetes, elevated glucose and free fatty acids can cause beta cell dysfunction, which raises the question whether elevated cholesterol induces beta cell dysfunction in this disease. Zainisha Vasanji’s research is aimed at determining whether exposure of beta cells to elevated cholesterol is the trigger for the chain of events that lead to islet amyloid formation in type 2 diabetes. Zainisha’s study may help delineate the cause of the beta cell defect in type 2 diabetes and may lead to new therapies to prevent the progressive loss of insulin secretion in this disease.