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

摘要

Aim: The effects of streptozotocin (STZ)-induced diabetes on oxidative energy metabolism of rat kidney mitochondria were examined at the end of 1 week and 1 month of STZ treatment. Methods: At the end of 1 week of induction of diabetes, respiration rates with pyruvate + malate and succinate as the substrates increased while those with beta-hydroxybutyrate and ascorbate + TMPD decreased. Respiration with glutamate was not affected. Insulin treatment had no alleviating effect. The changes persisted through 1 month of induction of diabetes and were not corrected by insulin treatment even at this stage. beta-hydroxybutyrate dehydrogenase activity registered significant decrease while the succinate dehydrogenase activity increased in diabetic and insulin-treated diabetic animals whereas only marginal changes were evident in the composition of the cytochromes. Results: The ATPase activity tended to be high in the diabetic groups and was restored by insulin treatment. At both the stages, i.e. early and late stages of diabetes the mitochondria were tightly coupled and the ADP/O ratios were in normal expected ranges. Conclusion: Taken together, the results suggest that kidney is the major target tissue to suffer impairment of mitochondrial function with the onset of the disease which persists throughout and that insulin treatment is ineffective in restoring the normal state.