Resveratrol improves glucose uptake in insulin-resistant adipocytes via Sirt1

Insulin resistance serves as "common soil" for promoting the development of metabolic diseases; however, the precise pathological factors leading to insulin resistance are not well clarified. Resveratrol (Res) is a natural polyphenolic compound with anti-inflammatory and antioxidative effects. However, effects and mechanisms of Res on glucose metabolism in adipocytes remain largely unknown. In this study, we show Res treatment significantly increases glucose uptake in insulin-resistant 3T3-L1 adipocytes in vitro. Mechanistically, Res up-regulates the protein level of Sirt1 that improves insulin signaling pathway and promotes cellular membrane Glut4 accumulation. Meanwhile, Sirt1 enhances phosphorylation level of AMPK which elevates p-AKT level. Consequently, the transcription factor FOXO1 translocalizes from nucleus to cytoplasm where protein degradation occurs. Therefore, the gene expression of resistin, a direct transcriptional target of FOXO1, is reduced and insulin sensitivity is improved. Importantly, we recapitulate the similar pattern of related protein changes in epididymal adipose tissues of insulin-resistant mice after Res intervention in vivo, reinforcing the hypothesis of Res being involved in regulation of glucose uptake via Sirt1-AMPK axis. Our findings clarify the beneficial effects of Res on glucose transportation in insulin-resistant adipocytes and involved pathway including Sirt1-AMPK, suggesting its potential therapeutic application in the treatment or prevention of insulin-resistance-related metabolic symptoms.