Molecular Basis for Faulty Lipid Metabolism in Diabetes

PGC-1-alpha is a global regulator of liver fat metabolism but is inactivated upon phosphorylation.

Results of several different groups of experiments by researchers from the University of Pennsylvania School of Medicine (Philadelphia, USA) published in the June 6, 2007, issue of the journal Nature confirmed that the action of insulin on Akt2/PKB triggered the phosphorylation of PGC-1-alpha. In the absence of insulin (as in diabetes) or Akt2/PKB, the liver displayed a pathogenic type of fat metabolism that contributed to the coronary artery disease that characterizes type 2 diabetes.

"Over the last 10 years, we have begun to understand the importance of fat metabolism in diabetes,” said senior author Dr. Morris J. Birnbaum, professor of diabetes and metabolic diseases at the University of Pennsylvania. "Type II 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. We hope that drug companies will look for new ways to modify fat metabolism in type two diabetics using these possible targets (PGC-1a and Akt2/PKB).”


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University of Pennsylvania School of Medicine