Voluntary running improves glucose tolerance and insulin resistance in female spontaneously hypertensive rats

We evaluated the effects of voluntary exercise training on glucose metabolism and measures of insulin sensitivity in female spontaneously hypertensive rats (SHR). Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. Exercising SHR were housed in running wheels for 8 weeks (SHRx8) or 16 weeks (SHRx16). At 22 weeks of age, we measured systolic blood pressure, performed oral glucose tolerance tests, and determined hexokinase activity and glucose transporter (GLUT) 4 content in skeletal muscle to assess intracellular glucose metabolism. Blood pressure was lower in WKY (139+/-12 mm Hg) than untrained SHR (216+/-13 mm Hg). Exercise training caused a reduction in blood pressure (-18 mm Hg) for SHRx8. After a brief (5-h) fast, serum glucose was lower in SHR that exercised compared with sedentary SHR, whereas insulin concentrations were identical between all SHR and WKY. Corresponding free fatty acids (FFA) were twofold higher in SHR than in WKY. In response to glucose, SHR demonstrated higher glucose and FFA responses, with exercise decreasing the glucose values in a dose-dependent manner. Although the insulin response was comparable in all groups, the glucose-to-insulin ratio was higher in SHR, indicating a relative insulin resistance for both glucose disposal and suppression of free fatty acids. Hexokinase activity and GLUT4 content were elevated 1.4- and 2.8-fold, respectively, in plantaris muscle of SHRx16, suggesting an improvement in the capacity for glucose transport and phosphorylation with exercise. These results provide evidence that voluntary running in female SHR lowers blood pressure and selectively increases glucose uptake and insulin action, but not suppression of FFA.