Abnormality Inside Muscle Cells Linked to Type 2 Diabetes

The Physicians Committee

Abnormality Inside Muscle Cells Linked to Type 2 Diabetes

February 12, 2004

Type 2 diabetes is, in large part, genetic. When the disease runs in families, even lean healthy children often have subtle abnormalities in their ability to metabolize sugar efficiently.

In the February 12, 2004, issue of the New England Journal of Medicine, Yale University researchers report on their comparisons of 14 young lean insulin-resistant individuals with 12 age-weight-activity matched insulin-sensitive controls. They found an abnormality in the mitochondria—the tiny organelles that act as powerhouses inside the cells of the body. Specifically, the problem appears to be due to a reduction in mitochondrial activity which may be due to a reduction in mitochondrial content in muscle cells, which, in turn, leads to a failure to metabolize fat properly. As fat builds up within muscle cells, it leads to insulin resistance by interfering with insulin signaling.

Even so, genes are not destiny. The tendency to develop diabetes manifests much more commonly in individuals who are overweight and sedentary than in those who are lean and physically active. The same authors have recently shown that activation of an enzyme called AMP kinase in muscle, which occurs with exercise, can lead to increased mitochondrial biogenesis.

Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med. 2004;350:664-671.

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