PMID- 30170066 OWN - NLM STAT- MEDLINE DCOM- 20190128 LR - 20190128 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 838 DP - 2018 Nov 5 TI - MicroRNA-17 impairs glucose metabolism in insulin-resistant skeletal muscle via repressing glucose transporter 4 expression. PG - 170-176 LID - S0014-2999(18)30499-0 [pii] LID - 10.1016/j.ejphar.2018.08.036 [doi] AB - Elimination of glucose transporter 4 (GLUT4) inevitably induces insulin resistance (IR), aggravating inflammation- and oxidative stress-related disorders. However, the underlying molecular mechanisms remain incompletely understood. In this study, we identified miR-17 as an important regulator of IR by targeting GLUT4. MiR-17 expression was found significantly elevated in skeletal tissues of rats with type 2 diabetes mellitus (T2DM), along with marked downregulation of GLUT4 protein level. Luciferase reporter gene assay demonstrated a direct interaction between miR-17 and the 3'untranslated region of GLUT4 mRNA. Correlation analyses (Spearman, Pearson, and Kendall) revealed that miR-17 level was negatively correlated with GLUT4 expression. Additionally, loss- and gain-of-function analyses showed that overexpression of miR-17 impaired glucose metabolism in L6 rat skeletal muscle cell line. In contrast, knockdown of endogenous miR-17 ameliorated glucose metabolism, accompanied by elevation of GLUT4 protein level. These findings unraveled a novel mechanism for IR that involves repression of GLUT4 by miR-17 and suggested miR-17 as a potential molecular target for the development of new therapeutic approaches for the treatment of T2DM. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. 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 - Zhou, Tong AU - Zhou T 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 - Lin, Yuan AU - Lin 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 - 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 - Xu, Chaoqian AU - Xu C AD - Mudanjiang Medical University, 157000, China. 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. 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. Electronic address: jennying223@126.com. 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. LA - eng PT - Journal Article DEP - 20180828 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Blood Glucose) RN - 0 (Glucose Transporter Type 4) RN - 0 (MIRN17 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (Slc2a4 protein, rat) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Blood Glucose MH - Carbohydrate Metabolism/genetics MH - Cell Line MH - Diabetes Mellitus, Type 2/blood/etiology/*genetics/metabolism MH - Diet, High-Fat/adverse effects MH - Disease Models, Animal MH - Down-Regulation MH - Gene Knockdown Techniques MH - Glucose/*metabolism MH - Glucose Transporter Type 4/blood/*genetics/metabolism MH - Humans MH - Insulin Resistance/*genetics MH - Male MH - MicroRNAs/genetics/*metabolism MH - Muscle, Skeletal/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - GLUT4 OT - Insulin resistance OT - MiR-17 OT - Skeletal muscle EDAT- 2018/09/01 06:00 MHDA- 2019/01/29 06:00 CRDT- 2018/09/01 06:00 PHST- 2018/04/08 00:00 [received] PHST- 2018/08/27 00:00 [revised] PHST- 2018/08/27 00:00 [accepted] PHST- 2018/09/01 06:00 [pubmed] PHST- 2019/01/29 06:00 [medline] PHST- 2018/09/01 06:00 [entrez] AID - S0014-2999(18)30499-0 [pii] AID - 10.1016/j.ejphar.2018.08.036 [doi] PST - ppublish SO - Eur J Pharmacol. 2018 Nov 5;838:170-176. doi: 10.1016/j.ejphar.2018.08.036. Epub 2018 Aug 28.