title: Ampelopsin Improves Insulin Resistance by Activating PPARγ and Subsequently Up-Regulating FGF21-AMPK Signaling Pathway.
abstract: Ampelopsin (APL), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. Here, we explored the anti-diabetic activity of APL and elucidate the underlying mechanism of this action. In palmitate-induced insulin resistance of L6 myotubes, APL treatment markedly up- regulated phosphorylated insulin receptor substrate-1 and protein kinase B, along with a corresponding increase of glucose uptake capacity. APL treatment also increased expressions of fibroblast growth factor (FGF21) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK), however inhibiting AMPK by Compound C or AMPK siRNA, or blockage of FGF21 by FGF21 siRNA, obviously weakened APL -induced increases of FGF21 and p-AMPK as well as glucose uptake capacity in palmitate -pretreated L6 myotubes. Furthermore, APL could activate PPAR γ resulting in increases of glucose uptake capacity and expressions of FGF21 and p-AMPK in palmitate -pretreated L6 myotubes, whereas all those effects were obviously abolished by addition of GW9662, a specific inhibitor of peroxisome proliferator- activated receptor -γ (PPARγ), and PPARγsiRNA. Using molecular modeling and the luciferase reporter assays, we observed that APL could dock with the catalytic domain of PPARγ and dose-dependently up-regulate PPARγ activity. In summary, APL maybe a potential agonist of PPARγ and promotes insulin sensitization by activating PPARγ and subsequently regulating FGF21- AMPK signaling pathway. These results provide new insights into the protective health effects of APL, especially for the treatment of Type 2 diabetes mellitus.
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wan
authors.affiliation: College of Basic Medical Sciences, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zou
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Qianyong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 400038, China.
authors.forename: Mantian
authors.initials: M
authors.lastname: Mi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005346:Fibroblast Growth Factors / Q000819:agonists / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D005419:Flavonoids; D047495:PPAR gamma; D034741:RNA, Small Interfering; C414620:fibroblast growth factor 21; C106407:ampelopsin; D005346:Fibroblast Growth Factors; D055372:AMP-Activated Protein Kinases; D005947:Glucose