Activation of Estrogen Receptor Is Crucial for Resveratrol-Stimulating Muscular Glucose Uptake via Both Insulin-Dependent and-Independent Pathways

OBJECTIVE—Estradiol (E2) is known to modulate insulin sensitivity and, consequently, glucose homeostasis. Resveratrol (RSV), an agonist of estrogen receptor (ER), has exerted antihy-perglycemic effects in streptozotocin-induced type 1 diabetic rats in our previous study and was also shown to improve insulin resistance in other reports. However, it remains unknown whether activation of ER is involved in the metabolic effects of RSV via insulin-dependent and-independent mechanisms. RESEARCH DESIGN AND METHODS—Male Sprague-Daw-ley rats were given a high cholesterol–fructose (HCF) diet for 15 weeks and were treated with RSV for either 15 days or 15 weeks. RESULTS—Here, we show that RSV shifts the metabolic char-acteristics of rats on an HCF diet toward those of rats on a standard diet. RSV treatment increased insulin-stimulated whole-body glucose uptake and steady-state glucose uptake of soleu