Resveratrol regulates neuronal glucose uptake and insulin sensitivity via P21-activated kinase 2 (PAK2).
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.
['Varshney|Pallavi|P|', 'Dey|Chinmoy Sankar|CS|']
D009327:4-Chloro-7-nitrobenzofurazan D055372:AMP-Activated Protein Kinases D000818:Animals D000975:Antioxidants D015153:Blotting, Western D002460:Cell Line D045744:Cell Line, Tumor D003847:Deoxyglucose D004305:Dose-Response Relationship, Drug D005947:Glucose D007328:Insulin D009474:Neurons D010766:Phosphorylation D051057:Proto-Oncogene Proteins c-akt D000077185:Resveratrol D013267:Stilbenes D054462:p21-Activated Kinases
Resveratrol Neuron Glucose uptake Insulin sensitivity PAK2