Endurance running exercise is an effective alternative to estradiol replacement for restoring hyperglycemia through TBC1D1/GLUT4 pathway in skeletal muscle of ovariectomized rats.

Menopause is a risk factor for impaired glucose metabolism. Alternative treatment of estrogen for postmenopausal women is required. The present study was designed to investigate the effects of 5-week endurance running exercise (Ex) by treadmill on hyperglycemia and signal pathway components mediating glucose transport in ovariectomized (OVX) placebo-treated rats, compared with 4-week 17β-estradiol (E2) replacement or pair-feeding (PF) to the E2 group. Ex improved the hyperglycemia and insulin resistance index in OVX rats as much as E2 or PF did. However, Ex had no effect on body weight gain in the OVX rats. Moreover, Ex enhanced the levels of GLUT4 and phospho-TBC1D1 proteins in the gastrocnemius of the OVX rats, but E2 or PF did not. Instead, the E2 increased the Akt2/AS160 expression and activation in the OVX rats. This study suggests that endurance Ex training restored hyperglycemia through the TBC1D1/GLUT4 pathway in muscle by an alternative mechanism to E2 replacement.