Diabetes is associated closely with the development of hypertension and coronary heart disease. The pathophysiological link between these diseases is a dysregulation of the vascular endothelial nitric oxide synthase (eNOS), an endothelial enzyme inducing vasodilation after phosphorylation at serine 1177. Physical activity has been shown to improve eNOS protein expression and regulation. 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.

Purpose of this pilot study was to examine differences in eNOS expression and phosphorylation between type 2 diabetic persons and non-diabetic controls as well as the effect of physical training on skeletal muscle eNOS in non-insulin dependent type 2 diabetic men.

Muscle biopsies were obtained from the M. vastus lateralis of nine 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.

At baseline, diabetic men had four times higher phosphorylated eNOS contents compared to the reference group. After the physical training, the proportion of phosphorylated eNOS in the diabetes-group cut in half before training , demonstrated by immunhistochemsitry . Western blot results showed an increased overall eNOS level while phosphorylated eNOS was significantly reduced after physical exercise.

In conclusion, eNOS Ser1177 seems to be hyperphosphorylated in skeletal muscle of type-2 diabetic men under basal conditions. Exercise improves eNOS protein expression and regulation not only in endothelial but also in skeletal muscle. Whether this may contribute to a restoration of mitochondrial dysregulation or a degradation of muscle has to be further investigated.