Diabetes' link to obesity broken in mice

St. Louis, Feb. 15, 2005 -- Scientists at Washington University School of Medicine in St. Louis used genetically modified mice to uncover a potentially important link between diabetes and obesity.

By genetically altering production of a factor found in skeletal muscle, scientists produced mice that can't get fat but do develop early signs of diabetes. Reversing the alteration produced mice that can become obese but do not develop diabetes.

The findings provide important insights for scientists struggling to find new ways to cope with the unprecedented epidemic of obesity now spreading through the United States and other nations. Obesity brings with it a range of health consequences including sharply increased risk of type 2 diabetes, the most common form of diabetes.

Scientists broke the link to improve their understanding of the network of factors that lead from obesity to the onset of diabetes. Based on what they learned, they applied a drug treatment in their new transgenic mice and in a different, previously established mouse line that suffers from obesity and a diabetes-like condition. In both groups, the drug increased insulin sensitivity, which is a primary goal of diabetes treatment.

"These results confirm that the links between obesity and diabetes show great promise as targets for new therapies that act as 'metabolic modulators' in muscle," says senior author Daniel P. Kelly, M.D., professor of medicine, of pediatrics and of molecular biology and pharmacology.

The study appears in the February 2005 issue of Cell Metabolism. It reveals new details of the activities of the peroxisome proliferator-activated receptors (PPARs), a family of receptors that affects the way cells respond to energy resources.

Diabetes disrupts the body's ability to manage energy resources including both fat and sugar. Insulin is a primary regulator of these resources. When the intake of calories exceeds the ability of the body to

Contact: Michael C. Purdy
Washington University School of Medicine

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