|本期目录/Table of Contents|

[1]盛菲,倪钰鸽,牛文彦.瑞帕利辛改善棕榈酸诱导的骨骼肌细胞胰岛素抵抗[J].天津医科大学学报,2024,30(04):338-342.[doi:10.20135/j.issn.1006-8147.2024.04.0338]
　SHENG Fei,NI Yuge,NIU Wenyan.Reparixin improves palmitic acid-induced insulin resistance in skeletal muscle cells[J].Journal of Tianjin Medical University,2024,30(04):338-342.[doi:10.20135/j.issn.1006-8147.2024.04.0338]
点击复制

瑞帕利辛改善棕榈酸诱导的骨骼肌细胞胰岛素抵抗(PDF)
分享到：

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
30卷
期数:
2024年04期
页码:
338-342
栏目:
基础医学
出版日期:
2024-07-10

文章信息/Info

Title:
Reparixin improves palmitic acid-induced insulin resistance in skeletal muscle cells
文章编号:
1006-8147(2024)044-0338-05
作者:
盛菲; 倪钰鸽; 牛文彦
（天津医科大学基础医学院免疫学系，天津300070）
Author(s):
SHENG Fei; NI Yuge; NIU Wenyan
（Department of Immunology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China）
关键词:
瑞帕利辛; 成肌细胞; 胰岛素抵抗; 细胞因子信号转导抑制因子3; 糖尿病
Keywords:
Reparixin;  myoblasts;  insulin resistance;  SOCS3;  diabetes mellitus
分类号:
R392.1
DOI:
10.20135/j.issn.1006-8147.2024.04.0338
文献标志码:
A
摘要:
目的：探讨瑞帕利辛（Reparixin）对棕榈酸（PA）诱导的C2C12成肌细胞胰岛素抵抗的影响。方法：CCK-8（cell counting Kit-8）法检测不同浓度的PA或Reparixin处理后C2C12成肌细胞活力；将C2C12成肌细胞分为牛血清白蛋白组（BSA组）、PA组、PA+Reparixin组，免疫印迹检测SOCS3蛋白水平及胰岛素信号分子蛋白激酶B（Akt）和160 kD的蛋白激酶B底物（AS160）磷酸化水平，qPCR检测SOCS3 mRNA水平。将C2C12-GLUT4myc小鼠成肌细胞同上分组，ELISA检测细胞GLUT4myc转位。结果：0、100、200、300 μmol/L的PA和0、20、30、40 μmol/L的Reparixin均不影响C2C12细胞活力。PA降低胰岛素磷酸化Akt和AS160的作用（均P＜0.000 1），Reparixin逆转PA的影响（F=86.78、264.6，P＜0.001，P＜0.000 1）。PA降低胰岛素促进GLUT4myc转位的作用（P＜0.001），Reparixin逆转PA的影响（F=41.4，P＜0.01）。PA上调SOCS3 mRNA（P＜0.001）和蛋白水平（P＜0.05），Reparixin逆转PA对SOCS3的影响（F=51.64、7.97，P＜0.001，P＜0.05）。结论：Reparixin可能通过下调SOCS3基因和蛋白表达，缓解棕榈酸诱导的小鼠C2C12成肌细胞胰岛素抵抗。
Abstract:
Objective： To investigate the effect of Reparixin on palmitic acid（PA）-induced insulin resistance in C2C12 myoblasts. Methods：The cell counting Kit-8（CCK-8） was used to detect the viability of C2C12 myoblasts treated with different concentrations of PA and Reparixin. C2C12 myoblastes were divided into bovine serum albumin group（BSA group），PA group and PA+Reparixin group，respectively. The expressions of suppressor of cytokine signaling 3（SOCS3） and the phosphorylation of insulin signaling molecules protein kinase B（Akt），protein kinase B substrate of 160 kD（AS160） were detected by Western blotting. The mRNA level of SOCS3 was detected by qPCR. C2C12-GLUT4myc myoblasts were grouped as above. The GLUT4myc translocation was detected by ELISA. Results：CCK-8 results showed that 0，100，200，300 μmol/L PA and 0，20，30，40 μmol/L Reparixin did not affect C2C12 cell viability. PA reduced insulin-stimulated Akt and AS160 phosphorylation（both P<0.000 1），which were reversed by Reparixin（F=86.78，264.6，P＜0.001，P＜0.000 1）. PA reduced GLUT4myc translocation（P<0.001） which was reversed by Reparixin（F=41.4，P<0.01）. PA increased the levels of SOCS3 mRNA（P<0.001） and SOCS3 protein（P<0.05），which were reversed by Reparixin（F=51.64，7.97，P<0.001，P<0.05）. Conclusion：Reparixin may alleviate PA-induced insulin resistance in C2C12 myoblasts by down-regulating SOCS3 expression.

参考文献/References:

[1] HU W，LI W，SUM W，et al. Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models[J].Pharmacol Res，2021，177（5）：105917.
[2] CALDER?譫N-DUPONTD，TORRE-VILLALVAZO I，D?魱AZ-VILLASE?譙OR A. Is insulin resistance tissue-dependent and substrate-specific? The role of white adipose tissue and skeletal muscle[J]. Biochimie，2023，204（1）：48-68.
[3] SANVEE G M ，PANAJATOVIC M V，BOUITBIR J，et al. Mechanisms of insulin resistance by simvastatin in C2C12 myotubes and in mouse skeletal muscle[J]. Biochem Pharmacol，2019，164：23-33.
[4] SONG H，HUANG Q，ZHANG Y，et al. Wheat germ peptide impro-ves glucose metabolism and insulin resistance in HepG2 hepatocytes via regulating SOCS3/IRS1/Akt pathway[J]. Nutr Res，2023， 120：135-144.
[5] UEKI K，KONDO T，KAHN C R，et al. Suppresor of cytokine signaling 1 （SOCS-1） and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms[J]. Mol Cell Biol，2004，24（12）：5434-5446.
[6] LEITNER J M，MAYR F B，FIRBAS C，et al. Reparixin，a specific interleukin-8 inhibitor，has no effects on inflammation during endotoxemia[J]. Int J Immunopathol Pharmacol，2007，20（1）：25-36.
[7] SHULMAN G I. Ectopic fat in insulin resistance，dyslipidemia，and cardiometabolic disease[J]. N Engl J Med，2014，371（12）：1131.
[8] CHABOWSKI A，ENDZIAN-PIOTROWSKA M，KONSTANTYNO-WICZ K，et al. Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes[J]. Acta Physiol，2013，207（2）：346-357.
[9] DAI H B，WANG H Y，WANG F Z，et al. Adrenomedullin ameliorates palmitic acid-induced insulin resistance through PI3K/Akt pathway in adipocytes[J]. Acta Diabetologica，2022，59（5）：661-673.
[10] KORBECKI J，BAJDAK-RUSINEK K. The effect of palmitic acid on inflammatory response in macrophages： an overview of molecular mechanisms[J]. Inflamm Res，2019，68（11）：915-932.
[11] DU H，DUAN S，LEI R，et al. Astragalin inhibits insulin resistance and oxidative Stress in palmitic acid-induced HepG2 cells[J]. Curr Top Nutraceut R，2022，20（4）：635-640.
[12] SAMUEL V T，SHULMAN G I. The pathogenesis of insulin resistance： integrating signaling pathways and substrate flux[J]. J Clin Invest，2016，126（1）：12-22.
[13] BOUCHER J，KLEINRIDDERS A，KAHN C R. Insulin receptor signaling in normal and insulin-resistant states[J].Cold Spring Harb Perspect Biol，2014，6（1）：a009191.
[14] WATSON R T，KANZAKI M，PESSIN J E. Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes[J].Endocr Rev，2004，25（2）：177-204.
[15] RICHTER E A，HARGREAVES M. Exercise，GLUT4，and skeletal muscle glucose uptake[J]. Physiol Rev，2013，93（3）：993-1017.
[16] KARNIELI E，ARMONI M. Transcriptional regulation of the insulin-responsive glucose transporter GLUT4 gene： from physiology to pathology[J]. Am J Physiol Endocrinol Metab，2008，295（1）：E38-E45.
[17] LETO D，SALTIEL A R. Regulation of glucose transport by insulin： traffic control of GLUT4[J]. Nat Rev Mol Cell Biol，2012，13（6）：383-396.
[18] WHITE C A，NICOLA N A. SOCS3： an essential physiological inhibitor of signaling by interleukin-6 and G-CSF family cytokines[J]. JAKSTAT，2013，2（4）：e25045.
[19] UEKI K，KONDO T，TSENG YH，et al. Central role of suppressors of cytokine signaling proteins in hepatic steatosis，insulin resistance，and the metabolic syndrome in the mouse[J]. Proc Natl Acad Sci U S A，2004，101（28）：10422-10427.
[20] O′CONNOR J C，SHERRY C L，GUEST C B，et al. Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3[J].J Immunol，2007，178（11）：6886-6893.
[21] WADA T，SUNAGA H，MIYATA K，et al. Aryl hydrocarbon receptor plays protective roles against high fat diet （HFD）-induced hepatic steatosis and the subsequent lipotoxicity via direct transcriptional regulation of socs3 gene expression[J]. J Biol Chem，2016，291（13）：7004-7016.

相似文献/References:

备注/Memo

备注/Memo:
基金项目：国家自然科学基金面上项目（82270856）
作者简介：盛菲（1998-），女，硕士在读，研究方向：免疫学；
通信作者：牛文彦，E-mail：wniu@tmu.edu.cn。
更新日期/Last Update: 2024-07-10