Heart mitochondrial NO production enhancement precedes mitochondrial biogenesis in Type 1 Diabetes Mellitus

Abstract

The aim was to study heart mitochondrial function in the early stages of Diabetes (DM) which was induced by a single dose of Streptozoticin (60 mg/kg,ip) in male Wistar rats. Glycemia was determined 72 h after injection (C:129±7; DM:456±34 mg/dl). Animals were sacrificed at day 10 and heart mitochondrial fraction was isolated. State 3 O2 consumption (11%), respiratory control ratios (17%), and complexes I-III (18%) and II-III (10%) activities were lower in diabetic than in control rats. Mitochondrial GSSG/GSH ratio was 10% higher in diabetic animals, indicating an imbalance in cellular redox state. Furthermore, linear correlations between the modified parameters and glycemia were observed, suggesting a close association between hyperglycemia and heart mitochondrial dysfunction. NO production rate was 22% higher in diabetic rats in accordance to the increase in mitochondrial NOS expression (79%). Heart mitochondrial mass and PGC 1α expression were similar in control and DM rats. To conclude, after 7 days of sustained hyperglycemia, heart mitochondrial dysfunction is observed in which NO production and mtNOS expression are significantly increased but mitochondrial biogenesis is not triggered yet, suggesting that mitochondrial NO is upstream de novo synthesis of mitochondria.