title: Potentiation of neuronal insulin signaling and glucose uptake by resveratrol: the involvement of AMPK.
abstract: Resveratrol (RSV), a polyphenolic phytoestrogen, has been shown to activate the serine/threonine kinase 5'-adenosine monophosphate-activated protein kinase (AMPK) and to stimulate insulin signaling and glucose uptake in skeletal muscle cells. A direct effect of RSV on neuronal insulin signaling, however, has not been demonstrated. Here, we report that RSV stimulates glucose uptake and potentiates insulin signaling in Neuro-2A (N2A) cells, which is characterized by the increased phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). Furthermore, RSV activates AMPK in N2A cells, which can be prevented using a specific pharmacological inhibitor, Compound C. Compound C abrogates RSV-induced Akt and GSK-3β phosphorylation and glucose uptake. Thus, we demonstrate that RSV potentiates insulin signaling and glucose uptake via AMPK activation in neuronal cells.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sec 67, S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Mayur I
authors.initials: MI
authors.lastname: Patel
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.forename: Chinmoy S
authors.initials: CS
authors.lastname: Dey
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007328:Insulin; D011720:Pyrazoles; D011743:Pyrimidines; D013267:Stilbenes; C516138:dorsomorphin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D000077185:Resveratrol