Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway. (5th July 2015)

• Record Type: Journal Article
• Authors: Shi, Linying; Zhang, Ting; Liang, Xinyu; Hu, Qin; Huang, Juan; Zhou, Yong; Chen, Mingliang; Zhang, Qianyong; Zhu, Jundong; Mi, Mantian
• Is Part Of: Molecular and cellular endocrinology. Volume 409(2015)
• Page Start: 92
• Page End: 102
• Publication Date: 2015-07-05
• Subjects: AMPK -- Autophagy -- Dihydromyricetin -- Skeletal muscle insulin resistance -- Type 2 diabetes; 2-NBDG 2-deoxy-2-[(7-nitro-2, 1, 3-benzoxadiazol-4-yl)amino]-D-glucose -- 3-MA 3-methyladenine -- AMP adenosine monophosphate -- AMPK AMP-activated protein kinase -- Atg autophagy-related gene -- ATP adenosine triphosphate -- BafA1 bafilomycin A1 -- CC compound C -- DHM dihydromyricetin -- DMSO dimethyl sulfoxide -- FFA free fatty acid -- GFP green fluorescent protein -- HPLC high performance liquid chromatography -- IRS-1 phosphorylated insulin receptor substrate-1 -- LC3 light chain 3 -- mTOR mammalian target of rapamycin -- SMIR skeletal muscle insulin resistance -- siRNA small interfering RNA; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.03.009
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: DHM significantly improved SMIR by inducing autophagy. DHM induced autophagy through activating AMPK signaling pathway in skeletal muscle myotubes. Abstract: Skeletal muscle insulin resistance (SMIR) plays an important role in the pathogenesis of type 2 diabetes. Dihydromyricetin (DHM), a natural flavonoid, exerts various bioactivities including anti-oxidative and hepatoprotective effects. Herein, we intended to determine the effect of DHM on SMIR and the underlying mechanisms. We found that DHM increased the expression of phosphorylated insulin receptor substrate-1, phosphorylated Akt and glucose uptake capacity in palmitate-treated L6 myotubes under insulin-stimulated conditions. The expression of light chain 3, Beclin 1, autophagy-related gene 5 (Atg5), the degradation of sequestosome 1 and the formation of autophagosomes were also upregulated by DHM. Suppression of autophagy by 3-methyladenine and bafilomycin A1 or Atg5 and Beclin1 siRNA abolished the favorable effects of DHM on SMIR. Furthermore, DHM increased the levels of phosphorylated AMP-activated protein kinase (AMPK) and Ulk1, and decreased phosphorylated mTOR levels. AMPK inhibitor compound C (CC) and AMPK siRNA abrogated DHM-induced autophagy, subsequently suppressed DHM-induced SMIR improvement. Additionally, DHM inhibited the activity of F1F0-ATPase thereby activating AMPK. Finally, the results of in vivo study conducted in high fat diet-fed rats were consistent with the findings of in vitro study. In conclusion, DHM improved SMIR by inducing autophagy via the activation of AMPK signaling pathway.