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Young people prone to type 2 diabetes exhibit alterations in mitochondrial activity

Researchers at Yale have found that decreased activity in muscle mitochondria, the powerhouses of the cell, may be a major factor in the development of type 2 diabetes in young, lean offspring of parents with the disease.

They demonstrated a potential mechanism for the accumulation of fat in muscle cells of young, lean, insulin-resistant children of parents with type 2 diabetes by comparing them with insulin-sensitive control subjects matched for age, weight, height and activity.

"There is a strong relationship between lipid content in the muscle and insulin resistance in skeletal muscle," said principal investigator Gerald I. Shulman, M.D., professor of internal medicine and cellular & molecular physiology at Yale School of Medicine. "Insulin resistance is the best predictor for whether someone will eventually develop type 2 diabetes."

Using proton magnetic resonance spectroscopy (MRS), a safe, noninvasive method that does not involve any ionizing radiation, researchers found that insulin resistance in muscle of the diabetic offspring was accompanied by an increase in muscle cell lipid content.

Shulman, an investigator at the Howard Hughes Medical Institute, led his group to distinguish whether the increase in muscle cell triglycerides was the result of increased delivery of fatty acids to muscle cells from the fat stored in "fat cells" (adipocytes), or the result of a decreased rate of fat oxidation by the mitochondria in the muscle cells. They measured rates of fatty acid release from adipocytes and found no differences between the two groups. In contrast, using phosphorus MRS they found a 30 percent reduction in the rate of mitochondrial energy production in the muscle of insulin resistant subjects compared to the control group.

"These data support the hypothesis that insulin resistance in young, lean, healthy insulin resistant offspring of patients with type 2 diabetes may be due to an inherited defe
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Contact: Karen N. Peart
karen.peart@yale.edu
203-432-1326
Yale University
16-Feb-2004


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