Colorado State University Biochemists Identify Saturated Fat Byproduct As Likely Contributor To Type 2 Diabetes

Research results posted on the Journal of Biological Chemistry's Web site at www.jbc.org show that a saturated fat metabolite called ceramide contributes to the development of insulin resistance in cultured cell experiments. Furthermore, the lab studies indicate that excess accumulation of ceramide in the body is a necessary link connecting saturated fats to insulin resistance. The entire research paper can be found on the Web site's papers in press section and is expected to be published in the journal's April print edition.

"Our research team is making great progress -- we have determined that ceramide is undeniably an important factor in the development of insulin resistance in muscle tissue," said Scott Summers, assistant professor in the Department of Biochemistry and Molecular Biology and principal investigator of the study. "These findings suggest that medication aimed to prevent ceramide accumulation in body tissue might lessen or even prevent insulin resistance and lead to breakthroughs in the treatment of type 2 diabetes."

Summers added that the next step for the Colorado State research team is to determine if they can produce the same results in more complicated models of insulin resistance, such as diabetic rodents. "If the same role for ceramide is proven in rodent models, we can then begin developing medications or forms of gene therapy to prevent ceramide accumulation in tissue cells and potentially eliminate the need for many diabetics to take insulin," he said.

Type 2 diabetes results from either a decreased discharge of insulin into the bloodstream or an inability of the released insulin to induce the necessary nutrient storage in body tissues. Summers' research focuses on the latter, where body cells essentially ignore insulin. As a result of insulin resistance, skeletal muscle and other tissues cannot absorb glucose appropriately, and blood glucose levels remain elevated in a state of hyperglycemia. If uncontrolled, this leads to a wasting of body tissues and death. Complications of prolonged hyperglycemia also include diseases of the eye, kidney and cardiovascular system.

Summers' research has been funded by grants from the American Diabetes Association, the National Institutes of Health, the American Heart Association and the March of Dimes. The research is of particular interest because more than 80 percent of type 2 diabetics are obese, but the precise link between increased body fat and the development of diabetes has remained a mystery. Previous studies indicate that the excessive intake of saturated fats could contribute to the development of type 2 diabetes. However, the Colorado State research is the first to show that a specific saturated fatty acid metabolite is responsible for insulin resistance.

"We speculated that saturated fats were not themselves responsible for antagonizing insulin action, but rather that some metabolite of the fats might be responsible for blocking insulin effects," said Jose Antonio Chavez, doctoral candidate on Summers' research team and lead author of the paper. "In lab studies, we incubated muscle tissue with saturated fats and used drugs to block the conversion of the fats into ceramide. This process completely prevented insulin resistance."

Chavez added that although abnormal ceramide accumulation is unlikely to account entirely for the diverse array of defects found in insulin-resistant tissues, the team's findings connect ceramide as a vital factor explaining some of the harmful effects that saturated fats have on the human body.

Diabetes accounts for about 15 percent of all health-care expenditures and totals more than $45 billion in direct medical costs each year in the United States. Type 2 diabetes is the most common form of the disease, 90 percent to 95 percent of all diabetics. Although children with the disease typically have type 1 diabetes, the rate of type 2 is rapidly rising among young people.

Insulin is a hormone in the body that stimulates the absorption and storage of carbohydrates and other nutrients in muscle and fat tissue. Following a meal, cells in the pancreas secrete insulin into the bloodstream which promotes the absorption and storage of carbohydrates and other nutrients in tissue while simultaneously suppressing glucose production by the liver. The inability of insulin to work effectively in peripheral tissues, mainly muscle, is termed insulin resistance.