My lab is focused on discovering physiological and cellular mechanisms that cause insulin resistance, diabetes, and obesity. In partnership with the Nestle Research Center in Lausanne, Switzerland, we are currently examining the effects of a whole grain versus refined grain diet on lean body mass, energy balance, and protein turnoveron body composition and energetics in overweight and obese adults.We have also teamed up with colleagues in our Bariatric Metabolic Institute and Department of Endocrinology, Metabolism and Diabetes, to determine how bariatric surgery can reverse type 2 diabetes. This work is funded by NIH and is examining the underlying cellular mechanisms that may explain diabetes remission after surgery. Our work combines clinical measures of insulin resistance (euglycemic hyperinsulinemic clamps, tracer isotopes, glucose tolerance testing), body composition (DEXA, CT scanning, MRI scanning) and exercise (VO2max testing), with cellular measures (protein and mRNA expression, enzyme activity, insulin signaling) in skeletal muscle, liver, pancreas, and adipose tissue samples. Our clinical studies are conducted in the CTSC-CRU, and bench analyses are performed in the LRI. In addition to our exercise/diet studies in obesity, type 2 diabetes and aging, we are currently working on research questions related to lipid-induced insulin resistance, energy metabolism and insulin resistance in conditions that include the metabolic syndrome, fatty liver disease, and obesity-related cancers. Work is also underway to develop a new in vitro model to measure the metabolic effects of contraction in muscle cells (exercise in a Petri dish!).
In other words ...
Lifestyle diseases such as obesity, type 2 diabetes, and fatty liver disease are widespread in our communities today. What can we do to reverse these diseases? Diet and exercise are obvious choices, but we still don't know the most effective and sustainable diet and exercise program to achieve this goal. Bariatric surgery is a more effective albeit slightly more radical approach to weight loss, and we have shown that it reverses type 2 diabetes in most patients. Surprisingly, bariatric surgery reverses type 2 diabetes before any significant weight loss. So, there is something about the surgery itself that lowers blood glucose. We are actively searching for the mechanism that produces this remarkable outcome. Discovering this mechanism will open the door to new and less invasive treatments for type 2 diabetes.
Schauer, P.R., S.R. Kashyap, K. Wolski, S.A. Brethauer, J.P. Kirwan, C.E. Pothier, S. Thomas, B. Abood, S.E. Nissen, D.L. Bhatt. Bariatric surgery versus intensive medical therapy in obese diabetic patients. N. Engl. J. Med., 366:1567-76, 2012.
Zein, C.O., R. Lopez, J.P. Kirwan, L.M. Yerian, S.L. Hazen, A.E. Feldstein, A.J. McCullough. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: New evidence on the potential therapeutic mechanism. Hepatology. 56:1291-9, 2012.
Malin, S.K., J.P. Kirwan. Fasting hyperglycemia blunts the regression of impaired glucose tolerance in older obese adults after lifestyle modification. Diabetes, Obes. Metab. 14:835-41, 2012.
Pagadela, M., T. Kasumov, A.J. McCullough, N.N. Zein, J.P. Kirwan. Role of ceramides in NAFLD. Trends Endocrinol Metab. 23:365-71, 2012.
Kirwan, J.P. Plasma ceramides target skeletal muscle in type 2 diabetes. Diabetes. 62:352-4, 2013.