Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle‐derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter‐4 (GLUT‐4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to clarify whether decreased muscle‐derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT‐4 signaling pathway in rats with type 2 diabetes. Male, 20‐week‐old, Otsuka Long‐Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF‐Con) and chronic resistance exercise (OLETF‐RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long‐Evans Tokushima Otsuka rats were used as the nondiabetic sedentary control group. OLETF‐Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT‐4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression. In contrast, OLETF‐RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT‐4/Akt signaling pathway. Moreover, chronic resistance exercise‐induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT‐4 translocation, and Akt phosphorylation. These findings suggest that the reduction in muscle‐derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes.

To clarify whether the relaxation period during stretching affects the degree of elevated shear rate and the degree of reduction of arterial stiffness, we examined relaxation duration to build an adequate stretching protocol. In Experiment 1, the changes in cardiac output, the shear rate in the posterior tibial artery, and blood volume in the calf muscle were measured during recovery (0–60 s) from a single bout of one-legged passive calf stretching in 12 healthy young men. In Experiment 2, the effects of different relaxation periods (5-, 10-, 20-, and 60-s) of passive one-legged intermittent calf stretching (30-s × 6 sets) on the femoral-ankle pulse wave velocity (faPWV) as an index of peripheral arterial stiffness were identified in 17 healthy young men. As a result, the stretched leg’s shear rate significantly increased from 0 to 10th s after stretching. The muscle blood volume in the stretched leg significantly reduced during stretching, and then significantly increased during the recovery period after stretching; however, cardiac output remained unchanged during stretching and recovery. Additionally, the reduction in faPWV from the pre-stretching value in the stretched leg was significantly larger in the protocol with 10-s and 20-s relaxation periods than that in the non-stretched leg, but this did not differ in the 5-s and 60-s relaxation periods. These findings suggest that the relaxation periods of intermittent static stretching that cause a high transient increase in shear rate (via reperfusion after microvascular compression by the stretched calf muscles) are effective to reduce arterial stiffness.

[Purpose] Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels affected the AT-induced reduction of arterial stiffness in middle-aged and older adults. [Methods] Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%–70% peak oxygen uptake [ ] for 45 min, 3 days/week). [Results] AT significantly increased ( p < 0.05) and decreased carotid β-stiffness ( p < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT ( p < 0.01). Additionally, no sex differences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stiffness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, p < 0.05), and the AT-induced increase in NOx/ADMA ratio was negatively correlated with a decrease in carotid β-stiffness (r = -0.514, p < 0.01). [Conclusion] These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.

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Introduction Regular aerobic exercise reverses aging-induced deterioration of arterial stiffness via an increased arterial nitric oxide (NO) production. Concurrently, asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by aerobic exercise training. A recent study showed that the NOx/ADMA ratio reflects endothelial function and may be an index of the states of cardiovascular disease. However, whether changes in the NOx/ADMA ratio by aerobic exercise training are associated with a decrease in arterial stiffness in healthy middle-aged and older male and female adults remains unclear. Purpose This study aimed to clarify whether the relationship between plasma ADMA and NOx levels affected aerobic exercise training-induced reduction of arterial stiffness in middle-aged and older adults. Additionally, we examined whether the effect of AT on circulating ADMA levels differed according to sex. Methods Thirty-one healthy middle-aged and older male and female subjects (male = 13, female = 18, 66.4±1.3 years) participated in the study. The subjects were randomly divided into 2 groups: a training group (n=16 [male = 6 / female = 10], 64.8±2.0 years) and a control group (n=15 [male = 7 / female = 8], 68.1±1.6 years). Subjects in the training group performed the AT program, which consisted of cycling on a leg ergometer at 60–70% of peak oxygen uptake (V(·)O2peak)for 45 min/day, 3 days/week for 8 weeks. Before and after the 8-week aerobic exercise training intervention, V(·)O2peak, plasma ADMA levels and plasma NOx levels were measured in all subjects. Also, carotid β-stiffness as an index of arterial stiffness was determined with ultrasonography. Results Aerobic exercise training significantly increased V(·)O2peak (P&lt;0.05) and decreased carotid b-stiffness (P&lt;0.01). Moreover, plasma ADMA levels were significantly decreased, and plasma NOx levels and NOx/ADMA ratio were significantly increased by aerobic exercise training (P&lt;0.01). Additionally, no sex differences in aerobic exercise training-induced changes in circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stiffness were observed. Furthermore, the aerobic exercise training-induced increase in circulating ADMA levels was negatively correlated with the increase in circulating NOx levels (r=−0.414, P&lt;0.05), and aerobic exercise training induced increase in NOx/ADMA ratio was negatively correlated with the decrease in carotid β-stiffness (r=−0.514, P&lt;0.01). Conclusion These results suggest that higher NOx/ADMA ratio affects aerobic exercise training-induced reduction of arterial stiffness, regardless of sex in middle-aged and older adults. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan