The two major lines of research interest of my laboratory are:
a) Determining the mechanism of intestinal and hepatic lipoprotein overproduction in insulin resistance and Type 2 diabetes. We perform studies in humans and in small animal models of insulin resistance, attempting to determine the molecular mechanisms whereby the liver and intestine overproduce lipoproteins in these conditions. We are currently examining the regulation of intestinal and hepatic lipoprotein particle production by hormones and inflammatory factors in humans, particularly as they pertain to the insulin resistant condition.
b) Determining the mechanism of high density lipoprotein (HDL) lowering in hypertriglyceridemic states such as insulin resistance and Type 2 diabetes. An additional major thrust of my laboratory has been to determine the mechanisms responsible for HDL lowering in hypertriglyceridemic states. Our current focus is on the mechanism whereby HDL triglyceride enrichment and interaction with hepatic lipase affects HDL clearance from the circulation.
Other lines of research interest are:
c)The effect of free fatty acids on pancreatic beta cell secretory function. In a series of in vivo experiments in humans and rats we have demonstrated lipotoxicity from elevated plasma free fatty acids on pancreatic beta cell function. We are currently examining the role of oxidant stress, ER stress and inflammation in mediating the deleterious effects of lipids on beta cell function.
d) In vivo studies in genetically altered mice investigating the mechanisms of insulin resistance, impairment of pancreatic beta cell function and mechanism of action of pharmacological agents. Some examples are:
i. Mechanism of action of dipeptidyl peptidase IV inhibitors
ii. The role of c-reactive protein (CRP) in modulating insulin action and secretion.
iii. CB1 receptor agonism and antagonism-differentiation of CNS from peripheral tissue-mediated beneficial metabolic effects.
Additional Appointments- Professor, Departments of Medicine and Physiology, University of Toronto
- Director, Division of Endocrinology and Metabolism, University of Toronto
- Canada Research Chair in Diabetes
