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Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway.
Mol Cell Endocrinol. 2015 Jul 05; 409:92-102.MC

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.

Authors+Show Affiliations

Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China. Electronic address: zjdnfs@126.com.Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing 400038, China. Electronic address: mi_mt2009@hotmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25797177

Citation

Shi, Linying, et al. "Dihydromyricetin Improves Skeletal Muscle Insulin Resistance By Inducing Autophagy Via the AMPK Signaling Pathway." Molecular and Cellular Endocrinology, vol. 409, 2015, pp. 92-102.
Shi L, Zhang T, Liang X, et al. Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway. Mol Cell Endocrinol. 2015;409:92-102.
Shi, L., Zhang, T., Liang, X., Hu, Q., Huang, J., Zhou, Y., Chen, M., Zhang, Q., Zhu, J., & Mi, M. (2015). Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway. Molecular and Cellular Endocrinology, 409, 92-102. https://doi.org/10.1016/j.mce.2015.03.009
Shi L, et al. Dihydromyricetin Improves Skeletal Muscle Insulin Resistance By Inducing Autophagy Via the AMPK Signaling Pathway. Mol Cell Endocrinol. 2015 Jul 5;409:92-102. PubMed PMID: 25797177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway. AU - Shi,Linying, AU - Zhang,Ting, AU - Liang,Xinyu, AU - Hu,Qin, AU - Huang,Juan, AU - Zhou,Yong, AU - Chen,Mingliang, AU - Zhang,Qianyong, AU - Zhu,Jundong, AU - Mi,Mantian, Y1 - 2015/03/20/ PY - 2014/12/08/received PY - 2015/03/12/revised PY - 2015/03/16/accepted PY - 2015/3/24/entrez PY - 2015/3/24/pubmed PY - 2016/2/10/medline KW - AMPK KW - Autophagy KW - Dihydromyricetin KW - Skeletal muscle insulin resistance KW - Type 2 diabetes SP - 92 EP - 102 JF - Molecular and cellular endocrinology JO - Mol. Cell. Endocrinol. VL - 409 N2 - 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. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/25797177/Dihydromyricetin_improves_skeletal_muscle_insulin_resistance_by_inducing_autophagy_via_the_AMPK_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(15)00140-9 DB - PRIME DP - Unbound Medicine ER -