Influence of exercise training on eNOS amount and phosphorylation in skeletal muscle of non-insulin dependent typ-2-diabetic men
Diabetes has been shown to go along with the development of hypertension and myocardial infarction. The pathophysiological link between the different diseases is a dysregulation of the vascular endothelial nitric oxide synthase (eNOS), an endothelial enzyme which induces vasodilation by the release of nitric oxide (NO) after being itself phosphorylated at serine 1177. Physical activity has been shown to improve eNOS protein expression and regulation by serine 1177. Less is known on eNOS-physiology and regulation in skeletal muscle, its alterations in diabetic persons and whether physical activity may influence skeletal muscle eNOS. The purpose of this pilot study was to find out whether there are differences in eNOS expression and phosphorylation between type 2 diabetic persons and non-diabetic controls and whether physical training may influence eNOS in the skeletal muscle of non-insulin dependent type 2 diabetic men.
Muscle biopsies were taken from the M. vastus lateralis of four male diabetic patients (65.3 ± 6.2 years, BMI: 29.4 ± 5.1) before and after a nordic-walking training intervention (2x/week for 3 months, heart frequency 120 – 130 bpm). The reference group consisted of five non-diabetic men (71.8 ± 2.04 years, BMI: 25.48 ± 1.30). Muscle biopsies were examined by immunohistochemistry or Western blot using antibodies against total and Ser1177-phosphorylated eNOS. The physical fitness-level was in the diabetes-group at 156 ± 31 watt power and 20.9 ± 6 rel. VO2max while the non-diabetics reached 140 ± 22 watt and 22.2 ± 5 rel. VO2max.
At baseline, the diabetics had shown four times higher phosphorylated eNOS contents compared with the reference group. After the physical training, the proportion of phosphorylated eNOS in the diabetes-group was about half as high as before training as obtained by immunohistochemical methods. Western blot results showed a raised total content but a reduced level of phosphorylated eNOS after physical exercise. Even the physical fitness-level rose with the intervention to 163 ± 25 watt power and 21,4 ± 6 rel. VO2max.
In conclusion, eNOS Ser1177 seems to be hyperphosphorylated in skeletal muscle of type-2 diabetic men. Exercise improves eNOS protein expression and regulation, which may counteract the degradation of muscle mass which has been described in type-2 diabetes.