PMID- 36195162 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20221208 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 193 IP - Pt 1 DP - 2022 Nov 20 TI - Proteomic analysis of skeletal muscle in Chinese hamsters with type 2 diabetes mellitus reveals that OPLAH downregulation affects insulin resistance and impaired glucose uptake. PG - 23-33 LID - S0891-5849(22)00619-0 [pii] LID - 10.1016/j.freeradbiomed.2022.09.029 [doi] AB - Type 2 diabetes mellitus (T2DM) is a metabolic disease controlled by a combination of genetic and environmental factors. The Chinese hamster, as a novel animal model of spontaneous T2DM with high phenotypic similarity to human disease, is of great value in identifying potential therapeutic targets for T2DM. Here, we used tandem mass tag (TMT) quantitative proteomics based on liquid chromatography-tandem mass spectrometry to assess the skeletal muscles of a Chinese hamster diabetes model. We identified 38 differentially abundant proteins, of which 14 were upregulated and 24 were downregulated. Further analysis of the differentially abundant proteins revealed that five of them (OPLAH, GST, EPHX1, SIRT5, ALDH1L1) were associated with oxidative stress; these were validated at the protein and mRNA levels, and the results were consistent with the proteomic analysis results. In addition, we evaluated the role of OPLAH in the pathogenesis of T2DM in human skeletal muscle cells (HSKMCs) by silencing it. The knockdown of OPLAH caused an increase in reactive oxygen species content, decreased the GSH content, inhibited the PI3K/Akt/GLUT4 signaling pathway, and reduced glucose uptake. We propose that OPLAH downregulation plays a role in insulin resistance and glucose uptake disorders in HSKMCs possibly via oxidative stress, making it a new therapeutic target for T2DM. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Shi, Zeya AU - Shi Z AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. FAU - Huo, Yitong AU - Huo Y AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. FAU - Hou, Jianan AU - Hou J AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. FAU - Zhang, Ruihu AU - Zhang R AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. FAU - Wu, Jianqin AU - Wu J AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. FAU - Wang, Wentao AU - Wang W AD - Department of Cardiology, The Affiliated Cardiovascular Disease Hospital of Shanxi Medical University, Taiyuan, 030001, China. FAU - Yu, Jingjing AU - Yu J AD - Experimental Animal Platform in Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China. FAU - Wang, Hailong AU - Wang H AD - School of Basic Medicine, Basic Medical Science Center, Shanxi Medical University, Jinzhong, 030600, China. FAU - Liu, Yu AU - Liu Y AD - Department of Pharmacology, Shanxi Medical University, Taiyuan, 030001, China. FAU - Song, Guohua AU - Song G AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. Electronic address: ykdsgh@163.com. FAU - Chen, Zhenwen AU - Chen Z AD - Beijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Science, Capital Medical University, Beijing, 100629, China. Electronic address: czwen@ccmu.edu.cn. FAU - Chen, Zhaoyang AU - Chen Z AD - Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, 030001, China. Electronic address: ccytycn@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221003 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - IY9XDZ35W2 (Glucose) RN - 0 (Insulin) SB - IM MH - Cricetinae MH - Animals MH - Humans MH - *Insulin Resistance/genetics MH - *Diabetes Mellitus, Type 2/metabolism MH - Cricetulus MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Proteomics MH - Down-Regulation MH - Muscle, Skeletal/metabolism MH - Glucose/metabolism MH - Insulin/metabolism OTO - NOTNLM OT - Chinese hamster OT - OPLAH OT - Proteomics OT - Skeletal muscle OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/10/05 06:00 MHDA- 2022/12/07 06:00 CRDT- 2022/10/04 19:13 PHST- 2022/06/30 00:00 [received] PHST- 2022/09/14 00:00 [revised] PHST- 2022/09/27 00:00 [accepted] PHST- 2022/10/05 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/10/04 19:13 [entrez] AID - S0891-5849(22)00619-0 [pii] AID - 10.1016/j.freeradbiomed.2022.09.029 [doi] PST - ppublish SO - Free Radic Biol Med. 2022 Nov 20;193(Pt 1):23-33. doi: 10.1016/j.freeradbiomed.2022.09.029. Epub 2022 Oct 3.