Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle cells

Abstract

Recent studies have suggested resveratrol (RSV) as a new natural therapeutic agent to treat type 2 diabetes and lipid-induced insulin resistance. Here, we investigated whether RSV could reverse palmitate-induced insulin resistance in human primary muscle cells. Myotubes obtained from six healthy men (54 ± 3 years (mean ± SE), BMI 25.0 ± 1.7 kg/m(2), fasting plasma glucose concentration (fP-glucose) 5.47 ± 0.09 mmol/l) were treated for 4 h with 100 μmol/l RSV and/or 0.2 mmol/l palmitate, and stimulated with or without 100 nmol/l insulin. Assays of glucose uptake, glycogen synthesis, palmitate oxidation, intracellular signalling and AMP-activated protein kinase (AMPK) activity were performed. RSV did not reverse palmitate-induced impairment of glucose metabolism. Surprisingly, RSV decreased glucose uptake and glycogen synthesis in human skeletal muscle cells. Palmitate oxidation and phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase β (ACCβ) were inhibited by RSV, and RSV completely blocked the activity of AMPK isoform complexes α1/β2/γ1 and α2/β2/γ1 in in-vitro kinase activity assays. Endoplasmic reticulum (ER) stress was increased in response to RSV, as indicated by increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) and increased expression of CCAAT/enhancer binding protein homologous protein (CHOP). Acute exposure to RSV inhibits AMPK activity, fatty-acid oxidation and glucose metabolism in human myotubes.