Resveratrol Action in the Duodenum and the Regulation of Insulin Sensitivity

Oral resveratrol improves insulin sensitivity in obese or diabetic rodents, but the underlying mechanisms remain elusive. Resveratrol's effects have been attributed, in part, to the activation of SIRT1 and/or AMPK in various tissues, although the low bioavailability of resveratrol raises questions about whether these effects are direct. We here show that intraduodenal resveratrol infusion activates duodenal SIRT1 and AMPK to enhance insulin sensitivity to lower glucose production (GP) in high-fat diet (HFD)-induced insulin resistance, while duodenal SIRT1 knockdown in chow fed-rats induces hepatic insulin resistance. The glucoregulatory role of preabsorptive resveratrol is dependent on a gut-brain neuronal network to remotely restore hypothalamic insulin sensitivity and GP regulation. Lastly, intraduodenal resveratrol infusion lowers GP and plasma glucose levels in two complementary obese and type 2 diabetic animal models. These studies highlight the therapeutic relevance of duodenal resveratrol and SIRT1/AMPK activation in improving insulin sensitivity and glucose control in obesity and diabetes.M.Sc.2018-02-28 00:00:0