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Joslin researchers identify new target for treatment of type 2 diabetes and prediabetes
Date:8/22/2011

BOSTON -- Aug. 22, 2011 -- Researchers at the Joslin Diabetes Center have shown that an enzyme found in the mitochondria of cells is decreased in the skeletal muscle of those with diabetes, a finding that could lead to the development of drugs to boost the activity of this enzyme in an effort to fight the disease.

A paper in published online today in the Proceedings of the National Academy of Sciences, showed that the enzyme, Sirt3, is decreased in the skeletal muscle of humans and animals with diabetes by at least half, compared to those without diabetes and that this may contribute to development of insulin resistance, one of the earliest manifestations of the disease. Sirt3 is found in the mitochondria, the power producers of cells that convert energy into usable forms.

"Ours is perhaps the first study to understand what is going wrong in the mitochondria of those with diabetes," said senior author C. Ronald Kahn, M.D., Head of the Joslin Section on Integrative Physiology and Metabolism and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. "Many studies have shown that the mitochondria don't work well in those with diabetes. This points to a cause of why they don't work well."

Dr. Kahn said the study sought to look at how decreased Sirt3 levels might affect the metabolism of cells, particularly how it could affect insulin action in cells. "We know that one of the hallmarks of early diabetes is insulin resistance in muscle, but we didn't know what caused it," he said.

He said the study showed that when Sirt3 levels are low, as they are in the case of diabetes, the mitochondria of the cells are not as efficient in energy metabolism as they should be.

When the mitochondria become inefficient, they generate what are known as reactive oxygen species (ROS), chemically reactive molecules containing oxygen, which create insulin resistance in the muscles, he said.

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Contact: Jeffrey Bright
jeffrey.bright@joslin.harvard.edu
Joslin Diabetes Center
Source:Eurekalert  

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