John Kirwan

Associate Professor

Ph.D. Ball State University, 1987
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RESEARCH DESCRIPTION

Dr. Kirwan’s lab focuses on the physiological and cellular mechanisms that underlie Insulin Resistance, Obesity and Type 2 Diabetes. He is currently conducting an NIH funded clinical trial (RO1 AG12834) to determine the effects of diet and exercise on Insulin Resistance in older, obese adults. The long-term goal is to identify new molecular targets in insulin resistance and obesity, coupled with new nutrition and exercise interventions that lead to effective treatments to delay morbidity and reduce mortality in the elderly.

Exercise training is typically associated with enhanced insulin sensitivity and is used as a first line treatment for age-related diseases such as type 2 diabetes. We have shown that heightened insulin sensitivity is mediated by increased post-receptor insulin signaling, specifically at the distal steps of the insulin/PI 3-kinase signaling cascade that leads to GLUT-4 translocation and glucose uptake.

We have also noted that while exercise generally exerts a positive effect on insulin sensitivity, it can paradoxically promote insulin resistance if it causes muscle damage. The mechanism associated with exercise induced insulin resistance appears to be related to TNF-?, which may phosphorylate specific serine residues at the level of the insulin receptor, and thus inhibit insulin signaling and glucose uptake in the muscle. Future studies will extend this work and also examine these mechanisms in elderly skeletal muscle.

Additional areas of active interest include the mechanism(s) underlying the reversal of Insulin Resistance in human skeletal muscle after exercise-training, and the effects of chronic low grade inflammation on the development of Insulin Resistance. Dr. Kirwan’s group works in collaboration with Dr. Art McCullough (Division of GI) in studying Insulin Resistance in NASH; and with Dr. Srinivasan Dasarathy examining the cellular mechanisms of skeletal muscle wasting.

RELATED RESEARCH AREAS

View John Kirwan's Publications on PubMed