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Dr. Martin Myers — A Headstrong Approach to Diabetes Research

Dr. Martin Myers

Diabetes represents one of the most common causes of death in the United States. It causes cardiovascular disease, kidney failure, blindness, and life-threatening infections, in addition to a plethora of other complications that decrease the length and quality of life of diabetic patients. Insulin resistance — in which the body fails to respond to insulin normally — underlies type 2 diabetes and complicates the treatment of many type 1 diabetics. Dr. Martin Myers, U-M’s Associate Professor of Internal Medicine and Associate Professor of Molecular and Integrative Physiology, conducts innovative research on insulin resistance. For the 15 million Americans who have diabetes, treating insulin resistance would extend and dramatically improve their lives.

Dr. Myers has personal as well as scientific reasons for his interest in diabetes — members of his family suffer from both forms of the disease. After earning his A.B. summa cum laude from Princeton University, Dr. Myers began studying diabetes as an M.D./ Ph.D student at Harvard Medical School, researching how insulin works at a molecular level in a laboratory at the Joslin Diabetes Center. After completing his doctoral degrees, he returned to the Joslin Diabetes Center as a faculty member, where he quickly received support from the Juvenile Diabetes Foundation, the American Diabetes Association and the National Institutes of Diabetes, Digestive and Kidney diseases of the National Institutes of Health, among others.

Dr. Myers moved to the University of Michigan in 2004 as a Michigan Biomedical Sciences Scholar. In 2005, he was elected to membership in the American Society for Clinical Investigation, which recognizes the accomplishments of the most outstanding young physician-scientists in the United States. He received the Jerome Conn Award for outstanding research and was promoted to Associate Professor of Internal Medicine and Molecular and Integrative Physiology in 2006. In March 2008, Dr. Myers was appointed the Marilyn H. Vincent Professor in Diabetes Research.

Dr. Myers’ research focuses on the processes that enable the body to respond normally to insulin, and how problems in these pathways contribute to the development of insulin resistance and diabetes. His laboratory specifically concentrates on the crucial role played by nerve centers in the unconscious part of the brain — what Myers calls "glycemic control centers" — that regulate the body’s ability to respond to insulin.

Insulin promotes the removal of sugar from the blood for storage in tissues and suppresses the production on sugar in the body. In type 1 diabetes the body stops producing insulin which results in high sugar levels in the blood. Therefore, those afflicted with type 1 require daily insulin injections to stay alive.

However, in type 2 diabetes, insulin resistance occurs. This is when the body does not respond to insulin properly, requiring increasing amounts of insulin to keep blood sugar at normal levels. The severe resistance in type 2 diabetes overwhelms the body’s ability to make enough insulin, resulting in increased blood sugar. Insulin resistance can also occur in patients with type 1 diabetes, and complicates their treatment by increasing the amount of insulin they must use.

Insulin resistance also renders islet transplantation ineffective, as the limited number of islets generally available for transplant cannot produce enough insulin to normalize blood sugar in the face of significant insulin resistance.

"In order to treat insulin resistance, we must first understand its causes. In order to understand its causes, we must first understand the processes in the body that allow insulin to 'get it right'," says Myers. This has been the crux of Myers’ research since his early days at the Joslin Diabetes Center, where he studied how insulin works via its receptor. It turns out that insulin does not work alone, however; a number of other important hormones and proteins that act in concert with insulin are required in order for the body to respond normally to insulin and to control blood sugar. Indeed, drugs based upon the hormones and proteins that facilitate insulin action have proven to be effective targets for the therapy of insulin resistance (in contrast to those directed at the insulin receptor, itself, which have not proved clinically useful to date).

Research from Dr. Myers’ laboratory and many others over the past decade has established that nerve centers in the unconscious part of the brain play important roles in facilitating insulin action and controlling blood sugar. These "glycemic control centers," which include the hypothalamus and brainstem, govern basic body functions such as heart rate, blood pressure, and hormone levels, as well as insulin action and blood sugar levels.

The Myers lab focuses on the actions of the key metabolic hormone, leptin. While best known for regulating body weight, leptin plays a crucial role in the regulation of insulin action and blood sugar via the glycemic control centers of the brain. Furthermore, much of the control of blood sugar by leptin is independent of the body weight control.

Myers has taken a comprehensive approach to understanding how leptin functions and regulates insulin sensitivity. Research in the Myers lab begins with understanding the mechanisms by which leptin acts at a molecular level, and then how these molecular mediators may contribute to the development of diabetes. Myers has examined two of these molecules in depth, showing that one is important for body weight, but not blood sugar control, and that another contributes to the development of insulin resistance. His laboratory is currently examining the two remaining molecular mediators, which may hold the key to the control of blood sugar and insulin sensitivity.

Furthermore, while most of the research on leptin action has focused on a single nerve center that accounts for about 20% of leptin action, Myers has begun to examine several other important nerve centers in order to understand the complete mechanism of leptin action. Ongoing work in the lab focuses on how several of these centers control the predisposition to insulin resistance and diabetes.

"Once we understand low leptin acts in these nerve centers and how they contribute to the regulation of blood sugar," says Myers, "we can learn how to regulate what they do in order to promote insulin sensitivity and treat diabetes."