Insulin status differentially affects energy transduction in cardiac mitochondria from male and female rats

Aim: The incidence of coronary heart diseases (CHD), congestive heart failure (CHF) and myocardial infarction is higher in diabetic patients than in non-diabetic groups, with these incidences being more in women than in the men. Hence, we examined involvement of mitochondrial energy transduction functions. Methods: Mitochondrial energy metabolism in cardiomyopathy was studied using streptozotocin (STZ)-diabetic male and female rats as the model system. Effects of insulin treatment were also evaluated. Results: The body and heart weights decreased in both male and female diabetic rats. Insulin treatments resulted in significant increase in the body and heart weights in the female rats. Mitochondrial respiration rates with all the substrates tested decreased in diabetic condition in both males and females. Treatment with two dose-regimens of insulin had differential restorative effect on mitochondrial substrate oxidation in the males but caused hyper-stimulation in the females. Diabetic state brought about 19% decrease in the cytochrome aa(3) content in the female rats. Treatment with 0.6 units of insulin significantly increased the cytochrome contents in general in both the sexes whereas higher dose (1.0 unit) caused decrease in the cytochromes content in the females. Diabetic state resulted in decreased dehydrogenases activities; insulin treatments had differential effect on the dehydrogenase activity in the males and the females. The results suggest that insulin treatment-induced hyper-stimulation of respiration in female rats may lead to increased production of reactive oxygen species. Besides, increased formation of advanced glycosylated end products may further lead to increased risk of CHF and CHD. Conclusions: The results suggest that differential effects of STZ-diabetes and insulin treatments in the female rats than in males may be the underlying cause for increased incidence of diabetic cardiomypathies in the females.