Effects of Endurance Training on the Skeletal Muscle Nitric Oxide Metabolism in Insulin-Independent Type 2 Diabetic Men-A Pilot Study

Background: Increases in the amount of inducible nitric oxide synthase (iNOS) protein and abnormal production of nitric oxide (NO) in skeletal muscle have been suggested to be associated with peripheral insulin resistance in patients with type 2 diabetes mellitus (T2DM). This pilot study analyzed whether a 3-month endurance training can affect iNOS protein and NO metabolite levels in the vastus lateralis muscle of insulin-independent T2DM men, thereby affecting the patients' glycemic control. Furthermore, serum molecules, which have been shown to activate iNOS protein expression in in vitro experiments, were quantified. Methods: Eight overweight/obese T2DM men (years = 61 +/- 10) participated in the study. Muscle biopsies and venous blood collections were performed at T1 (6 weeks before training), T2 (1 week before training), and T3 (3 to 4 days after training). Protein contents (iNOS) were determined by Western blotting, nitrite concentrations by chemiluminescence, and serum molecule levels by enzyme-linked immunosorbent assay kits. Results: The training reduced iNOS protein contents significantly (T2-T3: approximately -31%, P = 0.018). Nitrite concentrations as well as fasting glucose and HbA1c decreased, but not significantly. Serum tumor necrosis factor-a, thiobarbituric acid-reactive substances (lipid peroxidation as an indirect measure of reactive oxygen species), lipopolysaccharide binding protein, interferon-gamma, and interleuklin-1 beta showed no significant changes. Conclusions: The data indicate that the endurance training performed in the present study can reduce iNOS protein contents in insulin-independent T2DM men. Future studies should identify key molecules in iNOS regulation in vivo and fully clarify whether iNOS downregulation can help improve insulin sensitivity in T2DM patients in the long term.