Human studies in the 1990's showed that obese and insulin-resistant individuals had reduced muscle oxidative enzyme activity and decreased lipid metabolism compared with lean individuals (80–83); in 2002, it was shown that the skeletal muscle of obese individuals with type-2 diabetes (relative to lean normal controls) exhibited lower mitochondrial oxidoreductase activity and reduced mitochondrial number and size (84–86). The gene discussed is INS; the disease is type 2 diabetes mellitus.