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Ampelopsin Improves Insulin Resistance by Activating PPAR? 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 ? 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 -? (PPAR?), and PPAR?siRNA. Using molecular modeling and the luciferase reporter assays, we observed that APL could dock with the catalytic domain of PPAR? and dose-dependently up-regulate PPAR? activity. In summary, APL maybe a potential agonist of PPAR? and promotes insulin sensitization by activating PPAR? 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.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC4938387 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Ampelopsin Improves Insulin Resistance by Activating PPARγ and Subsequently Up-Regulating FGF21-AMPK Signaling Pathway.

Zhou Yong Y   Wu Ying Y   Qin Yu Y   Liu Lei L   Wan Jing J   Zou Lingyun L   Zhang Qianyong Q   Zhu Jundong J   Mi Mantian M  

PloS one 20160708 7


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  ...[more]

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