The Lewis lab has had a long interest in the mechanisms of various aspects of diabetic dyslipidemia, including postprandial lipemia, HDL lowering and hypertriglyceridemia. We have also had a long standing interest in the mechanisms of type 2 diabetes. Previously we have performed both animal and human mechanistic studies but currently are focusing exclusively on the human. In 2002, working in close collaboration with Dr. Khosrow Adeli (U of T), we made the novel observation that the intestine, in addition to the liver, overproduces lipoproteins in insulin resistant states. In our current funded work we are determining the mechanism of intestinal and hepatic lipoprotein overproduction in insulin resistance and Type 2 diabetes. We perform integrative, physiological studies in humans, attempting to determine the regulation of intestinal and hepatic lipoprotein particle production by hormones, nutrients and pharmacological agents. We have also received funding to study CNS regulation of systemic metabolism.