INCREASED EXPRESSION OF MITOCHONDRIAL-ENCODED GENES IN SKELETAL-MUSCLE OF HUMANS WITH DIABETES-MELLITUS

Screening subtraction libraries from normal and type II diabetic human skeletal muscle, we identified four different mitochondrially encoded genes which were increased in expression in diabetes. The genes were cytochrome oxidase I, cytochrome oxidase III, NADH dehydrogenase IV, a nd 12s rRNA, all of which are located on the heavy strand of the mitoc hondrial genome. There was a 1.5- to 2.2-fold increase in the expressi on of these mRNA molecules relative to total RNA in both type I and ty pe II diabetes as assessed by Northern blot analyses. Since there was similar to 50% decrease in mitochondrial DNA. copy number as estimated by Southern blot analyses, mitochondrial gene expression increased si milar to 2.5-fold when expressed relative to mitochondrial DNA copy nu mber. For cytochrome oxidase I similar changes in mitochondrial gene e xpression were observed in muscle of nonobese diabetic and ob/ob mice, models of type I and type II diabetes, respectively. By contrast ther e was no change or a slight decrease in expression of cytochrome oxida se 7a, a nuclear-encoded subunit of cytochrome oxidase, and the expres sion of mitochondrial transcription factor 1 in human skeletal muscle did not change with type I or type II diabetes. The increased mitochon drial gene expression may contribute to the increase in mitochondrial respiration observed in uncontrolled diabetes.