Abstract
Acute aerobic exercise (AE) increases skeletal muscle insulin sensitivity for several hours, caused by acute activation of AMP-activated protein kinase (AMPK). Acute resistance exercise (RE) also activates AMPK, possibly improving insulin-stimulated glucose uptake. However, RE-induced rapamycin-sensitive mechanistic target of rapamycin complex 1 (mTORC1) activation is higher and has a longer duration than after AE. In molecular studies, mTORC1 was shown to be upstream of insulin receptor substrate 1 (IRS-1) Ser phosphorylation residue, inducing insulin resistance. Therefore, we hypothesised that although RE increases insulin sensitivity through AMPK activation, prolonged mTORC1 activation after RE reduces RE-induced insulin sensitising effect. In this study, we used an electrical stimulation-induced RE model in rats, with rapamycin as an inhibitor of mTORC1 activation. Our results showed that RE increased insulin-stimulated glucose uptake following AMPK signal activation. However, mTORC1 activation and IRS-1 Ser632/635 and Ser612 phosphorylation were elevated 6 h after RE, with concomitant impairment of insulin-stimulated Akt signal activation. By contrast, rapamycin inhibited these prior exercise responses. Furthermore, increases in insulin-stimulated skeletal muscle glucose uptake 6 h after RE were higher in rats with rapamycin treatment than with placebo treatment. Our data suggest that mTORC1/IRS-1 signaling inhibition enhances skeletal muscle insulin-sensitising effect of RE.