Conclusion
Quercetin suppressed insulin-mediated glucose disposal in skeletal muscle tissue/cells under normal conditions while it ameliorated impaired glucose uptake under inflammatory conditions with activation of AMPK. In contrast, Q-3-G ameliorated insulin resistance in skeletal cells under inflammatory conditions without affecting glucose disposal under normal conditions.
Results
Under normal conditions, quercetin impaired glucose and insulin tolerance and attenuated insulin-mediated phosphorylation of Akt substrate of 160 kDa (AS160) and TBC1D1 without affecting Akt activity in male Institute of Cancer Research (ICR) mice. However, under inflammatory conditions, quercetin exhibited an opposite effect in these animals. In C2C12 cells, quercetin also decreased insulin-stimulated AS160 and TBC1D1 phosphorylation and glucose uptake in the absence of an inflammatory insult, whereas it improved the action of insulin under inflammatory conditions. Knockdown of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) blocked the differential effects of quercetin under both conditions. Unlike quercetin, Q-3-G had no influence on insulin-induced phosphorylation of AS160 and TBC1D1 and glucose uptake in C2C12 myotubes under normal conditions. Q-3-G displayed a similar regulation with quercetin in glucose disposal under inflammatory conditions.