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It all adds up: diabetes and oxidative stress

Medicine@Yale, 2010 - December

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We need oxygen, but it comes with a catch. Aerobic metabolism produces reactive oxygen species (ROS), which are toxic to mitochondria (one is pictured right), the “power plants” of cells.

Gerald I. Shulman, M.D., Ph.D., the George R. Cowgill Professor of Physiological Chemistry, has proposed that type 2 diabetes mostly affects older people because cumulative ROS-induced damage reduces mitochondrial activity, which predisposes older individuals to intracellular fat accumulation and insulin resistance — the major factor in the development of the disorder.

Shulman and colleagues engineered mice to express high levels of the antioxidant enzyme catalase in mitochondria to tamp down ROS. As reported in the December issue of Cell Metabolism, the mice were protected from age-related declines in energy metabolism, intracellular fat accumulation, and insulin resistance.

“It is estimated that 40 percent of the U.S. population over 65 has impaired glucose tolerance or type 2 diabetes. Targeting ROS in mitochondria may prevent and treat diabetes in these individuals,” Shulman says.

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