Penn Researchers Find Potential New Target for Type 2 Diabetes

(PHILADELPHIA) – Researchers at the University of Pennsylvania School of Medicine have discovered a potential new target for treating type 2 diabetes, according to a new study that appeared online this week in Nature. The target is a protein, along with its molecular partner, that regulates fat metabolism.

“Over the last 10 years, we have begun to understand the importance of fat metabolism in diabetes,” notes lead author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Diabetes and Metabolic Diseases at Penn and an Investigator of the Howard Hughes Medical Institute. “Type 2 diabetics are at a higher risk for cardiovascular disease because they also have disorders in fat metabolism as a result of obesity and abnormal insulin action.” Birnbaum is also the Associate Director of the Type 2 Diabetes Unit for Penn’s Institute for Diabetes, Obesity, and Metabolism.

When a person eats a meal, the pancreas usually responds by secreting insulin that signals the liver to stop making glucose and burning fat. When a type 2 diabetic eats a meal, insulin cannot stop the manufacture of glucose in the liver, but it can stop the burning of fat stores. This gives the diabetic person a “double whammy:” fatty acids accumulate from food and from the liver. Consequently, more fat is deposited in tissues and obesity worsens.

Until now there was no clear connection between insulin and the control of fat metabolism. This study shows that when insulin is present, as it is after a meal, the protein Akt2/PKB adds a phosphate group to its molecular partner PGC-1a. When this happens, PGC-1a cannot activate the genes needed for fat metabolism.

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