Insulin Attenuates Diabetes-Related Mitochondrial Alterations: A Comparative Study

P.   I.   Moreira; A.   P.   Rolo; C.      Sena; R.      Seica; C.   R.   Oliveira; M.   S.   Santos

Abstract

This study evaluated and compared the effect of insulin treatment on the status of brain, heart and kidney mitochondria isolated from 12-week streptozotocin (STZ)-induced diabetic rats versus STZ-diabetic animals treated with insulin during a period of 4 weeks. Mitochondria isolated from 12-week citrate (vehicle)-treated rats were used as control. Several mitochondrial parameters were evaluated: respiratory indexes (state 3 and 4 of respiration, respiratory control and ADP/O ratios), transmembrane potential, depolarization and repolarization levels, ATP, glutathione and coenzyme Q contents, production of hydrogen peroxide, superoxide dismutase, glutathione peroxidase and glutathione reductase activities and the ability of mitochondria to accumulate calcium. We observed that diabetes promoted a significant decrease in kidney and brain mitochondrial coenzyme Q9 content while this parameter was increased in heart mitochondria. Furthermore, diabetes induced a significant increase in hydrogen peroxide production in kidney mitochondria this effect being accompanied by a significant increase in glutathione peroxidase and reductase activities. Furthermore, brain mitochondria isolated from diabetic animals presented a lower ATP content and ability to accumulate calcium. In contrast, heart and kidney mitochondria presented a slight higher capacity to accumulate calcium. Insulin treatment normalized the levels of coenzyme Q9 and glutathione peroxidase and reductase activities and increased ATP content and the ability to accumulate calcium. Altogether these results suggest that insulin treatment attenuates diabetesinduced mitochondrial alterations protecting against the increase in oxidative stress and improving oxidative phosphorylation efficiency. In this line, insulin therapy, besides its well-known importance in the maintenance of glycemic control, may help to protect against mitochondrial dysfunction associated to several age-related disorders such as diabetes.

Keywords: Brain, diabetes, heart, insulin, kidney, mitochondria, oxidative stress, streptozotocin