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Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway.
Endocrine. 2015 Nov; 50(2):378-89.E

Abstract

Insulin resistance in skeletal muscle is a key feature in the pathogenesis of type 2 diabetes (T2D) that often manifests early in its development. Pharmaceutical and dietary strategies have targeted insulin resistance to control T2D, and many natural products with excellent pharmacological properties are good candidates for the control or prevention of T2D. Dihydromyricetin (DHM) is a natural flavonol which provides a wide range of health benefits including anti-inflammatory and anti-tumor effects. However, little information is available regarding the effects of DHM on skeletal muscle insulin sensitivity as well as the underlying mechanisms. In the present study, we found that DHM activated insulin signaling and increased glucose uptake in skeletal muscle in vitro and in vivo. The expression of light chain 3, the degradation of sequestosome 1, and the formation of autophagosomes were also upregulated by DHM. DHM-induced insulin sensitivity improvement was significantly abolished in the presence of 3-methyladenine, bafilomycin A1, or Atg5 siRNA in C2C12 myotubes. Furthermore, DHM increased the levels of phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), and Sirt3 in skeletal muscle in vitro and in vivo. Autophagy was inhibited in the presence of Sirt3 siRNA in C2C12 myotubes and in skeletal muscles from Sirt3-/- mice. Additionally, PGC-1α or AMPK siRNA transfection attenuated DHM-induced Sirt3 expression, thereby abrogating DHM-induced autophagy in C2C12 myotubes. In conclusion, DHM improved skeletal muscle insulin sensitivity by partially inducing autophagy via activation of the AMPK-PGC-1α-Sirt3 signaling pathway.

Authors+Show Affiliations

Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China. zjdnfs@126.com.Research Center for Nutrition and Food safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, 30th Gaotanyan Main Street, Shapingba District, Chongqing, 400038, People's Republic of China. mantianmi2012@163.com.

Pub Type(s)

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

Language

eng

PubMed ID

25896550

Citation

Shi, Linying, et al. "Dihydromyricetin Improves Skeletal Muscle Insulin Sensitivity By Inducing Autophagy Via the AMPK-PGC-1α-Sirt3 Signaling Pathway." Endocrine, vol. 50, no. 2, 2015, pp. 378-89.
Shi L, Zhang T, Zhou Y, et al. Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway. Endocrine. 2015;50(2):378-89.
Shi, L., Zhang, T., Zhou, Y., Zeng, X., Ran, L., Zhang, Q., Zhu, J., & Mi, M. (2015). Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway. Endocrine, 50(2), 378-89. https://doi.org/10.1007/s12020-015-0599-5
Shi L, et al. Dihydromyricetin Improves Skeletal Muscle Insulin Sensitivity By Inducing Autophagy Via the AMPK-PGC-1α-Sirt3 Signaling Pathway. Endocrine. 2015;50(2):378-89. PubMed PMID: 25896550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway. AU - Shi,Linying, AU - Zhang,Ting, AU - Zhou,Yong, AU - Zeng,Xianglong, AU - Ran,Li, AU - Zhang,Qianyong, AU - Zhu,Jundong, AU - Mi,Mantian, Y1 - 2015/04/21/ PY - 2015/01/13/received PY - 2015/04/05/accepted PY - 2015/4/22/entrez PY - 2015/4/22/pubmed PY - 2016/9/17/medline KW - Autophagy KW - Dihydromyricetin KW - Sirt3 KW - Skeletal muscle insulin sensitivity KW - Type 2 diabetes SP - 378 EP - 89 JF - Endocrine JO - Endocrine VL - 50 IS - 2 N2 - Insulin resistance in skeletal muscle is a key feature in the pathogenesis of type 2 diabetes (T2D) that often manifests early in its development. Pharmaceutical and dietary strategies have targeted insulin resistance to control T2D, and many natural products with excellent pharmacological properties are good candidates for the control or prevention of T2D. Dihydromyricetin (DHM) is a natural flavonol which provides a wide range of health benefits including anti-inflammatory and anti-tumor effects. However, little information is available regarding the effects of DHM on skeletal muscle insulin sensitivity as well as the underlying mechanisms. In the present study, we found that DHM activated insulin signaling and increased glucose uptake in skeletal muscle in vitro and in vivo. The expression of light chain 3, the degradation of sequestosome 1, and the formation of autophagosomes were also upregulated by DHM. DHM-induced insulin sensitivity improvement was significantly abolished in the presence of 3-methyladenine, bafilomycin A1, or Atg5 siRNA in C2C12 myotubes. Furthermore, DHM increased the levels of phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), and Sirt3 in skeletal muscle in vitro and in vivo. Autophagy was inhibited in the presence of Sirt3 siRNA in C2C12 myotubes and in skeletal muscles from Sirt3-/- mice. Additionally, PGC-1α or AMPK siRNA transfection attenuated DHM-induced Sirt3 expression, thereby abrogating DHM-induced autophagy in C2C12 myotubes. In conclusion, DHM improved skeletal muscle insulin sensitivity by partially inducing autophagy via activation of the AMPK-PGC-1α-Sirt3 signaling pathway. SN - 1559-0100 UR - https://www.unboundmedicine.com/medline/citation/25896550/Dihydromyricetin_improves_skeletal_muscle_insulin_sensitivity_by_inducing_autophagy_via_the_AMPK_PGC_1α_Sirt3_signaling_pathway_ L2 - https://dx.doi.org/10.1007/s12020-015-0599-5 DB - PRIME DP - Unbound Medicine ER -