Polyphenols Activate Energy Sensing Network in Insulin Resistant Models

Unhealthy diet deficient in fruits and vegetables but rich in calories is considered to be one factor responsible for the increased prevalence of insulin resistance and type 2 diabetes (T2D). The consumption of fast foods and soft drinks increases fructose consumption per se and this is of major concern since prolonged fructose intake induces insulin resistance and thereby T2D. The energy homeostasis is regulated by a network consisting of "fuel gauze" called AMP-activated protein kinase (AMPK), the NAD dependent type III deacetylase (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) which is disrupted in T2D. The present study was aimed to investigate the action of naringenin and quercetin on energy sensing molecules in insulin resistant models. L6 myotubes and albino Wistar rats were rendered insulin resistant with palmitate and fructose respectively. Naringenin, quercetin or metformin were used for treatment. Fructose and palmitate treatment resulted in insulin resistance as evidenced by decreased glucose transporter 4 (GLUT4) translocation. The translocation of GLUT4, phosphorylation of AMPK and the expression of SIRT1 and PGC-1α which were reduced in insulin resistant cells, were increased upon treatment with polyphenols. Further, naringenin and quercetin showed binding affinity with energy sensing molecules. We conclude that drugs from natural resources that target energy sensing molecules might be helpful to prevent insulin resistance.