Da. Antonetti et al., INCREASED EXPRESSION OF MITOCHONDRIAL-ENCODED GENES IN SKELETAL-MUSCLE OF HUMANS WITH DIABETES-MELLITUS, The Journal of clinical investigation, 95(3), 1995, pp. 1383-1388
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.