Winnick Laboratory

In humans, the liver plays a central role in the regulation of blood glucose homeostasis; consuming the sugar and storing it as glycogen during the fed state, then releasing it back into the blood on a need-basis when fasting. Unfortunately, these processes become dysfunctional in some people, thereby leading to diabetes, which, if left uncontrolled, can hasten the development of micro- and macro-vascular disease.

The research that my colleagues and I perform revolves around the study of how hepatic glucose metabolism is regulated in both the healthy and diseased states. As such, one area of focus is hypoglycemic counter-regulation. In preliminary animal studies, we showed that an acute increase in liver glycogen content can augment hepatic glucose production (HGP) in response to insulin-induced hypoglycemia. As a result, current NIH-funded studies are underway to investigate the translational potential of this finding to healthy humans and to people with type 1 diabetes whose counter-regulatory responses to hypoglycemia are diminished.

Chronic exercise training, with and without weight loss, can lower fasting HGP and improve blood glucose homeostasis in people with type 2 diabetes. Accordingly, a second arm of the research that we perform relates to the whole-body mechanisms responsible for these improvements and the study of how the intrahepatic pathways that contribute to HGP respond to lifestyle modification.

Finally, there is now overwhelming evidence demonstrating that Roux-en-Y gastric bypass (RYGB) surgery not only leads to significant weight loss in people who are obese, but also markedly improves blood glucose homeostasis in people with type 2 diabetes. The two primary metabolic improvements, as a result of RYGB, include increased insulin responsiveness to a mixed meal and lowered fasting HGP. Hence, we are interested in better understanding the mechanisms leading to reduced HGP after RYGB in people with type 2 diabetes as well as the effect that the increased insulin responsiveness has on the liver.