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T.H. Reynolds, assistant professor of health and exercise sciences at Â鶹Æƽâ°æ, has received a grant of nearly $370,000 from the National Institutes of Health to study a novel anti-obesity agent that improves insulin action. His work could lead to a reduction in the number of cases of Type 2 diabetes. 

Totaling $367,437, the funds are distributed through the National Institute of Diabetes and Digestive and Kidney Diseases.

The grant, the third that Reynolds has received from the NIH over seven years, will allow him to continue to explore the puzzle of Type 2 diabetes. As obesity has increased and the number of Type 2 diabetes cases has grown over the past three decades, public health officials have warned that an "epidemic" of diabetes is looming. In earlier research, Reynolds explored factors that regulate insulin action in skeletal muscle. Increased understanding of these factors are leading to the development of new treatment options, including novel anti-obesity and insulin-sensitizing compounds.

For the current study, Reynolds has zeroed in on genes that regulate weight and insulin metabolism. He has identified a receptor, Rev-ERBα, as a potential anti-obesity target. He wants to explore how certain substances, such as porphyrins, interact with Rev-ERBα to alter metabolism. By manipulating molecules in a process that involves overriding Rev-ERBα's natural job as a gene switch, Reynolds hopes to determine if disrupting the regular work of Rev-ERBα can lead to healthier lives. His preliminary data has shown increased insulin sensitivity and weight loss can result from such manipulation.

Explains Reynolds, "Rev-ERBα is a transcription factor?a protein that interacts with a cell's DNA. Our evidence has shown that it represses genes involved in energy metabolism and insulin action." He is hoping to harness Rev-ERBα and redirect it to activate genes that combat obesity, which could lead to improved insulin action in the body.

Reynolds became interested in researching Type 2 diabetes after recognizing the profound effect of exercise on reducing the incidence of the disease. He said, "I developed a passion for understanding how interventions like diet or exercise can improve a person's chance of avoiding disease. Exercise reverses insulin resistance and can lead to weight loss, but it is hard to do consistently." He added, "Exercise is almost a magic bullet to improve insulin sensitivity, but it doesn't come in a pill, which is hard for some people."

The grant, to be paid over three years, is an NIH Academic Research Enhancement Award and will support the work of undergraduate student collaborators. Reynolds hopes to have a team of three or four students as research assistants during the summer and to allow their work to continue during the academic year through independent study or thesis projects.

He's enthusiastic about the chance to help develop a new generation of biomedical scientists. He already has a remarkable record of success on that front: six Â鶹Æƽâ°æ students who have worked with him over the past five years have pursued graduate studies at schools such as the University of Pennsylvania, Cornell University, and the University of Michigan. Said Reynolds, "My greatest success is in what my students achieve through their research and their development as scientists."