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UAB research identifies two genes linked to insulin resistance

New research from UAB identifies two genes that may play a role in insulin resistance, opening a new avenue for researchers searching for treatments for Type 2 diabetes and metabolic syndrome. In findings published this week in the Journal of Biological Chemistry, the UAB team found that two genes, NR4A3 and NR4A1, seem to boost insulin sensitivity in muscle tissue.

Insulin lowers blood glucose, or sugar, by moving it from the bloodstream into skeletal muscle where it is metabolized for energy or stored for later use. Type 2 diabetes results from either a shortage of insulin or from de-sensitized muscle that does not respond well to insulin, allowing elevated glucose levels to remain in the blood stream. The latter is called insulin resistance.

Our findings show that these two proteins help sensitize muscle to insulin, promoting glucose uptake and thus keeping glucose levels within healthy limits, said Timothy Garvey, M.D., professor and chair of the Department of Nutrition Sciences at UAB and the lead investigator of the study. This gives science a new target for diabetes research by suggesting new pathways for drug development that will help boost the presence or activity of NR4A3 and NR4A1.

Garvey and colleague Yuchang Fu, Ph.D., assistant professor of nutrition sciences, also found that both genes were under-expressed in animal models with diabetes, leading to increased insulin resistance.

In simple terms, the abundant presence of these proteins in the body is a positive factor for avoiding diabetes, while their absence is associated with increased incidence of the disease, Garvey said. By better understanding the biologic underpinnings of the disease, we can begin to find novel therapeutic targets to decrease insulin resistance.

Garvey said the next step will be a methodical search of promising molecules that may interact with and promote the presence of NR4A3 and NR4A1.

There are more than 20 million Americans living with diabetes, 7 percent of the population. According to the National Institutes of Health, the incidence of diabetes is likely to increase due to the aging U.S. population and to the prevalence of obesity in America, both of which are risk factors for diabetes.

According to recent estimates from the Centers for Disease Control and Prevention, diabetes will affect one in three people born in 2000 in the United States. The prevalence of diagnosed diabetes in the United States is expected to increase 165 percent by 2050. Diabetes is widely recognized as one of the leading causes of death and disability in America.