Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long-Evans Tokushima Fatty rats

Abstract

Insulin-mediated glucose disposal is dependent on the vasodilator effects of insulin. In type 2 diabetes, insulin-stimulated vasodilation is impaired as a result of an imbalance in NO and ET-1 production. We tested the hypothesis that chronic voluntary wheel running (RUN) prevents impairments in insulin-stimulated vasodilation associated with obesity and type 2 diabetes independent of the effects of RUN on adiposity by randomizing Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia-induced obesity and type 2 diabetes, to 1) RUN, 2) caloric restriction (CR; diet adjusted to match body weights of RUN group), or 3) sedentary control (SED) groups (n = 8/group) at 4 wk. At 40 wk, NO- and ET-1-mediated vasoreactivity to insulin (1-1,000 μIU/ml) was assessed in the presence of a nonselective ET-1 receptor blocker (tezosentan) or a NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)], respectively, in second-order arterioles isolated from the white portion of the gastrocnemius muscle. Body weight, fasting plasma glucose, and hemoglobin A1c were lower in RUN and CR than SED (P < 0.05); however, the glucose area under the curve (AUC) following the intraperitoneal glucose tolerance test was lower only in the RUN group (P < 0.05). Vasodilator responses to all doses of insulin were greater in RUN than SED or CR in the presence of a tezosentan (P < 0.05), but group differences in vasoreactivity to insulin with coadministration of L-NAME were not observed. We conclude daily wheel running prevents obesity and type 2 diabetes-associated declines in insulin-stimulated vasodilation in skeletal muscle arterioles through mechanisms that appear to be NO mediated and independent of attenuating excess adiposity in hyperphagic rats.

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

“…This finding is consistent with previous data from our group showing that insulin-stimulated dilation in skeletal muscle arterioles was enhanced in WR, but not DR, OLETF rats (37). Herein, we also report that differences in insulin-stimulated vasorelaxation between WR and SED rats were largely abolished after treatment of aortic rings with a nonselective ET-1 receptor blocker.…”

Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

“…This impairment can be overcome by contractile exercise, which acutely augments both capillary recruitment and insulinmediated glucose uptake in muscle (9,34). Moreover, exercise training in normal and insulin-resistant rats has been shown to improve insulin-mediated glucose uptake, capillary recruitment, and NO-mediated vasodilation, suggesting that exercise potentiates vascular insulin sensitivity as well (17,19).…”

Poor Wheel-Running Exercise Can Decrease Blood Pressure through Hormonal Control and Increase Endurance Exercise Capacity in Middle-Aged Normal Rats

“…Likewise, voluntary WR was reported to increase NO formation and to decrease plasma angiotensin II concentration, and consequently, attenuated the elevation of systolic BP in SHRs [15]. In addition, positive immunostaining for phospho-specific eNOS in cross sections of white gastrocnemius muscle was increased in OLETF rats with voluntary WR [18]. Thus, a WR-induced reduction in resting BP appears to be ascribable in part to peripheral vascular resistance decreased by enhanced endothelium-dependent vasodilation, which is mediated via the NO signaling pathway.…”