INS and obesity due to melanocortin 4 receptor deficiency: In the present study, resveratrol improved insulin-mediated signal transduction [insulin-stimulated phosphorylation of IRS1 (Tyr632), Akt (Ser473), and TBC1D4 (Thr642)] in the myotubes from lean individuals, but not in the myotubes from individuals with severe obesity (Figs. 2 and 3).