Effect of streptozotocin-induced diabetes on oxidative energy metabolism in rat liver mitochondria-A comparative study of early and late effects.

The reports in the literature on effects of diabetes on mitochondrial energy-linked functions are conflicting. Hence we carried out systematic studies to evaluate the effects at the early and the late stages of the disease using STZ-diabetic rat as a model. At the end of one week, after induction of diabetes, respiration rates with glutamate and succinate as the substrates increased; respiration rates with other substrates e.g. β-hydroxybutyrate, pyruvate + malate and ascorbate + TMPD were not affected despite substantial decrease in the β-hydroxybutyrate dehydrogenase activity and cytochrome b and c+c(1) contents. Insulin treatment brought about increase in the cytochrome contents beyond control values. The ATPase activity was generally low in the diabetic animals and was not restored by insulin treatment.At the end of one month, the respiratory activities with all the substrates were generally low. Insulin treatment either restored or stimulated the respiration rates beyond control values. The content of cytochromes was differentially affected in the diabetic animals, but insulin treatment caused significant increase beyond control levels. The pattern for ATPase activity was similar to the early effects.At both the stages i.e. early and late stages of diabetes the mitochondria were tightly coupled. The ADP/O ratios were in normal expected ranges and the respiratory control ratios were comparable with the control groups. Insulin treatment resulted in apparent restoration of respiratory activity. However, the effects on the cytochromes and dehydrogenases activities were differential. Taken together the two observations would suggest that the mitochondria were not re-instated to normality despite apparent restoration of respiratory function.