Early hyperglycemia following alloxan administration in vivo is not associated with altered hepatic mitochondrial function: acceptable model for type 1 diabetes?

Abstract

Alloxan and oxidative stress, which have been detected in livers of laboratory animals shortly after in vivo alloxan administration, cause in vitro mitochondrial dysfunction, thus questioning alloxan diabetes as an acceptable model for type 1 diabetes, a model that cannot legitimately be used to investigate mitochondrial metabolism in a diabetic state. In the current study, the blood glucose concentration increased in the drug-treated group of Sprague–Dawley rats (compared with the placebo group) 45 or 60 min after alloxan treatment, whereas at 30 min the blood glucose concentration was unchanged. State 4, state 3, respiratory control, efficiency of oxidative phosphorylation, and mitochondrial ATP synthase activity, assayed using glutamate plus malate, pyruvate plus malate, or succinate as a substrate, were not negatively altered during the entire study. These results indicated that early increases of blood glucose concentration, after in vivo alloxan administration, did not lead to liver mitochondrial dysfunction, suggesting that alloxan diabetes can be used for the study of liver mitochondrial respiration in a diabetic state.