Advertisement

Environmental Science and Pollution Research

, Volume 25, Issue 23, pp 22400–22407 | Cite as

MicroRNA-191, acting via the IRS-1/Akt signaling pathway, is involved in the hepatic insulin resistance induced by cigarette smoke extract

  • Qianlei Yang
  • Yan Cui
  • Fei Luo
  • Xinlu Liu
  • Qiushi Wang
  • Jun Bai
  • Faqin Dong
  • Qian Sun
  • Lu Lu
  • Hui Xu
  • Junchao Xue
  • Chao Chen
  • Quanyong Xiang
  • Qizhan Liu
  • Qingbi Zhang
Interface Effect of Ultrafine Mineral Particles and Microorganisms

Abstract

Cigarette smoke causes insulin resistance, which is associated with type 2 diabetes mellitus (T2DM). However, the mechanism by which this occurs remains poorly understood. Because the involvement of microRNAs (miRNAs) in the development of insulin resistance is largely unknown, we investigated, in hepatocytes, the roles of miR-191 in cigarette smoke extract (CSE)-induced insulin resistance. In L-02 cells, CSE not only decreased glucose uptake and glycogen levels but also reduced levels of insulin receptor substrate-1 (IRS-1) and Akt activation, effects that were blocked by SC79, an activator of Akt. CSE also increased miR-191 levels in L-02 cells. Furthermore, the inhibition of miR-191 blocked the decreases of IRS-1 and p-Akt levels, which antagonized the decreases of glucose uptake and glycogen levels in L-02 cells induced by CSE. These results reveal a mechanism by which miR-191 is involved in CSE-induced hepatic insulin resistance via the IRS-1/Akt signaling pathway, which helps to elucidate the mechanism for cigarette smoke-induced T2DM.

Keywords

Cigarette smoke miRNA-191 Hepatic insulin resistance Akt IRS-1 

Abbreviations

CSE

Cigarette smoke extract

T2DM

Type 2 diabetes mellitus

IRS-1

Insulin receptor substrate-1

Akt,

Serine/threonine kinase;

PKB,

Protein kinase B;

3’-UTR,

3’-Untranslated region;

FBS,

Fetal bovine serum;

GAPDH,

Glyceraldehyde 3-phosphate dehydrogenase;

qRT-PCR,

Quantitative real-time polymerase chain reaction;

ANOVA,

Analysis of variance;

LSD,

Least significant difference

Notes

Acknowledgements

The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA), an experienced, English-speaking scientific editor for editing.

Funding

This work was supported by the Natural Science Foundations of China (81573199, 41130746, and 41472046); Luzhou-Southwest Medical University (2017LZXNYD-J23); and the Priority Academic Program Development of Jiangsu Higher Education Institutions (2014).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no competing interests.

References

  1. American Diabetes A (2004) Diagnosis and classification of diabetes mellitus. Diabetes Care 27(Suppl 1):S5–S10Google Scholar
  2. American Diabetes A (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37(Suppl 1):S81–S90CrossRefGoogle Scholar
  3. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefGoogle Scholar
  4. Bergman BC, Perreault L, Hunerdosse D, Kerege A, Playdon M, Samek AM, Eckel RH (2012) Novel and reversible mechanisms of smoking-induced insulin resistance in humans. Diabetes 61:3156–3166CrossRefGoogle Scholar
  5. de la Monte SM, Tong M, Agarwal AR, Cadenas E (2016) Tobacco smoke-induced hepatic injury with steatosis, inflammation, and impairments in insulin and insulin-like growth factor signaling. J Clin Exp Pathol 6:269Google Scholar
  6. Eliasson B, Taskinen MR, Smith U (1996) Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance. Circulation 94:878–881CrossRefGoogle Scholar
  7. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98CrossRefGoogle Scholar
  8. Feskens EJ, Kromhout D (1989) Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Stud Am J Epidemiol 130:1101–1108CrossRefGoogle Scholar
  9. Fu X, Dong B, Tian Y, Lefebvre P, Meng Z, Wang X, Pattou F, Han W, Wang X, Lou F, Jove R, Staels B, Moore DD, Huang W (2015) MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest 125:2497–2509CrossRefGoogle Scholar
  10. Hennessy E, O'Driscoll L (2008) Molecular medicine of microRNAs: structure, function and implications for diabetes. Expert Rev Mol Med 10:e24CrossRefGoogle Scholar
  11. Hutvagner G, Zamore PD (2002) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:2056–2060CrossRefGoogle Scholar
  12. Iribarren C, Tekawa IS, Sidney S, Friedman GD (1999) Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men. N Engl J Med 340:1773–1780CrossRefGoogle Scholar
  13. Jung HA, Ali MY, Bhakta HK, Min BS, Choi JS (2016) Prunin is a highly potent flavonoid from Prunus davidiana stems that inhibits protein tyrosine phosphatase 1B and stimulates glucose uptake in insulin-resistant HepG2 cells. Arch Pharm Res 40:37–48Google Scholar
  14. Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846CrossRefGoogle Scholar
  15. Leclercq IA, Da Silva MA, Schroyen B, Van Hul N, Geerts A (2007) Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J Hepatol 47:142–156CrossRefGoogle Scholar
  16. Li P et al (2016) Hematopoietic-derived galectin-3 causes cellular and systemic insulin resistance. Cell 167(973–984):e12Google Scholar
  17. Liu X, Luo F, Ling M, Lu L, Shi L, Lu X, Xu H, Chen C, Yang Q, Xue J, Li J, Zhang A, Liu Q (2016) MicroRNA-21 activation of ERK signaling via PTEN is involved in arsenite-induced autophagy in human hepatic L-02 cells. Toxicol Lett 252:1–10CrossRefGoogle Scholar
  18. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408CrossRefGoogle Scholar
  19. Lu L, Luo F, Liu Y, Liu X, Shi L, Lu X, Liu Q (2015) Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial-mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract. Toxicol Appl Pharmacol 289:276–285CrossRefGoogle Scholar
  20. Lu XL, Liu Y, Luo F, Zhang AH, Liu XL, Lu L, Shi L, Li J, Xue JC, Xu H, Fan WM, Liu QZ (2016) MicroRNA-21 activation of Akt via PTEN is involved in the epithelial-mesenchymal transition and malignant transformation of human keratinocytes induced by arsenite. Toxicol Res-Uk 5:1140–1147CrossRefGoogle Scholar
  21. Luo F, Sun B, Li H, Xu Y, Liu Y, Liu X, Lu L, Li J, Wang Q, Wei S, Shi L, Lu X, Liu Q, Zhang A (2016) A MALAT1/HIF-2alpha feedback loop contributes to arsenite carcinogenesis. Oncotarget 7:5769–5787Google Scholar
  22. Lykken EA, Li QJ (2016) The microRNA miR-191 supports T cell survival following common gamma chain signaling. J Biol Chem 291:23532–23544CrossRefGoogle Scholar
  23. Marx J (2002) Unraveling the causes of diabetes. Science 296:686–689CrossRefGoogle Scholar
  24. Mi Y, Qi G, Fan R, Qiao Q, Sun Y, Gao Y, Liu X (2017) EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF. FASEB J.  https://doi.org/10.1096/fj.201700400RR
  25. Nitulescu GM, Margina D, Juzenas P, Peng Q, Olaru OT, Saloustros E, Fenga C, Spandidos D, Libra M, Tsatsakis AM (2016) Akt inhibitors in cancer treatment: the long journey from drug discovery to clinical use (Review). Int J Oncol 48:869–885CrossRefGoogle Scholar
  26. Nogueiras R, Dieguez C, Lopez M (2015) Come to where insulin resistance is, come to AMPK country. Cell Metab 21:663–665CrossRefGoogle Scholar
  27. Park SY, Jeong HJ, Yang WM, Lee W (2013) Implications of microRNAs in the pathogenesis of diabetes. Arch Pharm Res 36:154–166CrossRefGoogle Scholar
  28. Perry IJ, Wannamethee SG, Walker MK, Thomson AG, Whincup PH, Shaper AG (1995) Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men. BMJ 310:560–564CrossRefGoogle Scholar
  29. Petersen KF, Shulman GI (2006) New insights into the pathogenesis of insulin resistance in humans using magnetic resonance spectroscopy. Obesity 14(Suppl 1):34S–40SCrossRefGoogle Scholar
  30. Saltiel AR, Pessin JE (2002) Insulin signaling pathways in time and space. Trends Cell Biol 12:65–71CrossRefGoogle Scholar
  31. Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148:852–871CrossRefGoogle Scholar
  32. Schroeder SA, Warner KE (2010) Don’t forget tobacco. N Engl J Med 363:201–204CrossRefGoogle Scholar
  33. So EY, Ouchi T (2014) BRAT1 deficiency causes increased glucose metabolism and mitochondrial malfunction. BMC Cancer 14:548CrossRefGoogle Scholar
  34. Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, Heim MH, Stoffel M (2011) MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 474:649–653CrossRefGoogle Scholar
  35. Wang PX, Zhang XJ, Luo P, Jiang X, Zhang P, Guo J, Zhao GN, Zhu X, Zhang Y, Yang S, Li H (2016) Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling. Nat Commun 7:10592CrossRefGoogle Scholar
  36. Wu Y, Song P, Zhang W, Liu J, Dai X, Liu Z, Lu Q, Ouyang C, Xie Z, Zhao Z, Zhuo X, Viollet B, Foretz M, Wu J, Yuan Z, Zou MH (2015) Activation of AMPKalpha2 in adipocytes is essential for nicotine-induced insulin resistance in vivo. Nat Med 21:373–382CrossRefGoogle Scholar
  37. Xu W, Ji J, Xu Y, Liu Y, Shi L, Liu Y, Lu X, Zhao Y, Luo F, Wang B, Jiang R, Zhang J, Liu Q (2015) MicroRNA-191, by promoting the EMT and increasing CSC-like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells. Mol Carcinog 54(Suppl 1):E148–E161CrossRefGoogle Scholar
  38. Yang WM, Jeong HJ, Park SW, Lee W (2015) Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes. Mol Nutr Food Res 59:2303–2314CrossRefGoogle Scholar
  39. Yin Y, Hua H, Li M, Liu S, Kong Q, Shao T, Wang J, Luo Y, Wang Q, Luo T, Jiang Y (2016) mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR. Cell Res 26:46–65CrossRefGoogle Scholar
  40. Zhao H, Huang X, Jiao J, Zhang H, Liu J, Qin W, Meng X, Shen T, Lin Y, Chu J, Li J (2015) Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-alpha-induced hepatic insulin resistance. Sci Rep 5:18093CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Qianlei Yang
    • 1
  • Yan Cui
    • 2
  • Fei Luo
    • 1
  • Xinlu Liu
    • 1
  • Qiushi Wang
    • 3
  • Jun Bai
    • 2
  • Faqin Dong
    • 4
  • Qian Sun
    • 1
  • Lu Lu
    • 1
  • Hui Xu
    • 1
  • Junchao Xue
    • 1
  • Chao Chen
    • 1
  • Quanyong Xiang
    • 3
  • Qizhan Liu
    • 1
  • Qingbi Zhang
    • 2
  1. 1.Institute of Toxicology, School of Public HealthNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.School of Public HealthSouthwest Medical UniversityLuzhouPeople’s Republic of China
  3. 3.Jiangsu Center for Disease Control and PreventionNanjingPeople’s Republic of China
  4. 4.Key Laboratory of Solid Waste Treatment and the Resource RecycleSouthwest University of Science and TechnologyMianyanPeople’s Republic of China

Personalised recommendations