title: Resveratrol regulates neuronal glucose uptake and insulin sensitivity via P21-activated kinase 2 (PAK2).
abstract: We have recently reported P21-activated kinase 2 (PAK2), a serine/threonine kinase as a negative regulator of neuronal glucose uptake and insulin sensitivity. Resveratrol (RSV), a natural polyphenol with anti-oxidative, anti-inflammatory and anti-diabetic properties, regulates PAK2 activity in HepG2 and ESC-B5 cell apoptosis. However, regulation of PAK2 by RSV in neuronal insulin signaling pathway, if any, is still unknown. In the present study, RSV treatment significantly increased PAK2 activity under insulin-sensitive and insulin-resistant condition, along with a marked decrease in glucose uptake in differentiated N2A cells. Pretreatment with AMPK inhibitor, followed by RSV treatment resulted in reduction in PAK2 activity whereas glucose uptake showed an increase. However, pretreatment with Akt inhibitor and then RSV exposure significantly increased PAK2 activity, with a corresponding decrease in glucose uptake. RSV treatment increased AMPK activity and decreased Akt activity. In conclusion, RSV negatively regulates neuronal glucose uptake and insulin sensitivity via PAK2.
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi 110016, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Varshney
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi 110016, India. Electronic address: csdey@bioschool.iitd.ac.in.
authors.forename: Chinmoy Sankar
authors.initials: CS
authors.lastname: Dey
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D007328:Insulin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007328:Insulin; D013267:Stilbenes; D003847:Deoxyglucose; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D055372:AMP-Activated Protein Kinases; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; D000077185:Resveratrol
keywords: Glucose uptake; Insulin sensitivity; Neuron; PAK2; Resveratrol