Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway

Molecular and Cellular Endocrinology
Linying ShiMantian Mi

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 condu...Continue Reading

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Citations

Jun 3, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shihui ChenMantian Mi
Jun 10, 2015·Molecular and Cellular Endocrinology·Qicheng ZhouMantian Mi
Jul 2, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Qiurong Wang, Jun Ren
Apr 2, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xianjuan KouNing Chen
Dec 15, 2015·Journal of Dental Research·Y H LeeH K Yi
Jun 27, 2018·Antioxidants & Redox Signaling·Francesca GiampieriMaurizio Battino
Jun 6, 2019·Photodermatology, Photoimmunology & Photomedicine·Shi WuDaxiang Lu
Sep 19, 2019·Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry·Humaira B NoorMd A T Sagor
Oct 17, 2017·Journal of Exercise Nutrition & Biochemistry·Do Keun ChoJoon Yong Cho
Sep 28, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Hongliang LiLonghuo Wu
Apr 18, 2018·Journal of Cellular Physiology·Kiana Hosseinpour-MoghaddamAmirhossein Sahebkar
Dec 19, 2016·Apoptosis : an International Journal on Programmed Cell Death·Peiqi WangLixia Chen
Nov 28, 2020·World Journal of Gastroenterology : WJG·Quan-Cheng ChengWei-Guang Zhang
Sep 18, 2020·European Journal of Medicinal Chemistry·Bhargav A PatelBrian S J Blagg
Aug 29, 2019·Journal of Agricultural and Food Chemistry·Yijia JiaShengbao Cai

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