PMID- 31004884 OWN - NLM STAT- MEDLINE DCOM- 20190828 LR - 20190828 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 59 DP - 2019 Jun TI - Emodin improves glucose metabolism by targeting microRNA-20b in insulin-resistant skeletal muscle. PG - 152758 LID - S0944-7113(18)30575-0 [pii] LID - 10.1016/j.phymed.2018.11.018 [doi] AB - BACKGROUND: Emerging evidence has indicated the therapeutic potential of emodin with its multiple pharmacological effects. PURPOSE: To evaluate role of emodin in regulating insulin resistance (IR) and to elucidate the underlying molecular mechanisms. STUDY DESIGN/METHODS: Fasting blood glucose (FBG) and lipid levels were measured before and after intragastric administration of emodin in type 2 diabetes mellitus (T2DM) rats. Glucose consumption was determined in L6 cells to investigate the effect of emodin on glucose metabolism. Expression of miR-20b and SMAD7 was quantified by real-time PCR for mRNAs or western blot analysis for proteins. RESULTS: Emodin ameliorated hyperglycemia and dyslipidemia in T2DM rats, and glucose metabolism in a concentration- and time-dependent manner. MiR-20b was markedly upregulated in the setting of IR and overexpression of miR-20b disrupted glucose metabolism by repressing SMAD7 in L6 cells. Knockdown of this miRNA produced the opposite effects. Emodin abolished the abnormal upregulation of miR-20b and indirectly upregulated SMAD7. CONCLUSION: Emodin improves glucose metabolism to produce anti-IR effects, and downregulation of miR-20b thereby upregulation of SMAD7 is an underlying mechanism for the beneficial effects of emodin. CI - Copyright (c) 2018. Published by Elsevier GmbH. FAU - Xiao, Dan AU - Xiao D AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Hu, Yingying AU - Hu Y AD - Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, China. FAU - Fu, Yujie AU - Fu Y AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Wang, Rui AU - Wang R AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Zhang, Haiying AU - Zhang H AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Li, Mingqi AU - Li M AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Li, Zhange AU - Li Z AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Zhang, Ying AU - Zhang Y AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Xuan, Lina AU - Xuan L AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Li, Xin AU - Li X AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Xu, Chaoqian AU - Xu C AD - Mudanjiang Medical University, 157000, China. FAU - Zhang, Yong AU - Zhang Y AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China; Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150086, China. Electronic address: hmuzhangyong@hotmail.com. FAU - Yang, Baofeng AU - Yang B AD - Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China; Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, the University of Melbourne, Melbourne, 3010, Australia. Electronic address: yangbf@ems.hrbmu.edu.cn. LA - eng PT - Journal Article DEP - 20181116 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Glucose Transporter Type 4) RN - 0 (Insulin) RN - 0 (RNA, Messenger) RN - 0 (Smad7 Protein) RN - 0 (Smad7 protein, rat) RN - IY9XDZ35W2 (Glucose) RN - KA46RNI6HN (Emodin) SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy/*metabolism MH - Down-Regulation/drug effects MH - Emodin/*pharmacology/therapeutic use MH - Glucose/*metabolism MH - Glucose Transporter Type 4/metabolism MH - Hyperglycemia/metabolism/prevention & control MH - Insulin/*metabolism MH - *Insulin Resistance MH - Male MH - Muscle, Skeletal/*drug effects/metabolism MH - *RNA, Messenger/metabolism MH - Rats MH - Smad7 Protein/metabolism MH - Up-Regulation/drug effects OTO - NOTNLM OT - Emodin OT - Insulin resistance OT - SMAD7 OT - Skeletal muscle OT - miR-20b EDAT- 2019/04/21 06:00 MHDA- 2019/08/29 06:00 CRDT- 2019/04/21 06:00 PHST- 2018/08/28 00:00 [received] PHST- 2018/10/27 00:00 [revised] PHST- 2018/11/15 00:00 [accepted] PHST- 2019/04/21 06:00 [pubmed] PHST- 2019/08/29 06:00 [medline] PHST- 2019/04/21 06:00 [entrez] AID - S0944-7113(18)30575-0 [pii] AID - 10.1016/j.phymed.2018.11.018 [doi] PST - ppublish SO - Phytomedicine. 2019 Jun;59:152758. doi: 10.1016/j.phymed.2018.11.018. Epub 2018 Nov 16.