Grant: Operating Grant-PA: INMD Start Up Funds (bridge funding) - New Investigators

Type 2 diabetes (T2D) mellitus is a global epidemic and an economic burden on society currently affecting more than 3 million Canadians. T2D results from malfunction of, damage, or loss of insulin producing pancreatic beta cells, which are found in the islets of Langerhans in the pancreas. It has been known for a long time that type 1 diabetes (classically juvenile onset diabetes) occurs when a patient's own immune system kills the insulin producing beta cells. I have been involved in recent research suggesting that the body's own immune system also contributes to beta cell malfunction in T2D (classically adult onset diabetes) via chronic inflammation. We are investigating how and why the immune system goes awry in T2D, resulting in harm to the insulin producing beta cell. Published studies to date and our preliminary studies suggest that the classic immune cell, the macrophage, participates in islet inflammation in T2D. Macrophages can hinder normal tissue function, or can actually promote the healing and regeneration of a tissue after it has been damaged. I have shown that there are more macrophages in damaged pancreatic islets in patients with T2D, but we don't know what effect they have on the normal function of beta cells, and if these cells can be targeted to treat diabetes. Here I propose to fill this knowledge gap. I will characterize how macrophages affect beta cell insulin secretion and survival in a culture dish, and the underlying mechanisms involved. I will characterize the role of macrophages during T2D progression in animal models of this disease. Finally, I will demonstrate that increasing numbers of "healing" macrophages can be used to treat T2D. Since current therapies for T2D do not target the cause of beta cell failure and are not able to stop ongoing beta cell failure, this knowledge should assist in devising new strategies to halt and reverse beta cell failure in T2D.