A schematic representation of the proposed mechanisms by which resveratrol improves insulin sensitivity. Working through the energy-sensing AMPK, resveratrol (RSV) may act to increase mitochondrial β-oxidation, which in turn increases the NAD+-to-NAHD ratio, triggering the activation of SIRT1 and the deacetylation of PGC-1α and resulting in mitochondrial biogenesis. AMPK-α1 and -α2–dependent increases in fatty acid oxidation and mitochondrial capacity decrease reactive lipid intermediates such as diacyglycerol (DAG) and ceramides, thereby improving insulin-stimulated glucose disposal. Ac, acetylation; ACC, acetyl-CA carboxylase; Akt, protein kinase B; CPT-1, carnitine palmitoyl transferase; IKK, inhibitor of κ kinase; FA, fatty acid; IRS-1, insulin receptor substrate-1; JNK, Jun NH2-terminal kinase; GCN5, histone acetyltransferase GCN5; P, phosphate; PP2A, protein phosphatase 2A; PDK, 3-phosphoinositide-dependent kinase; PKC, protein kinase C; TAG, triacylglycerol.