MicroRNA-191, acting via the IRS-1/Akt signaling pathway, is involved in the hepatic insulin resistance induced by cigarette smoke extract
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.
KeywordsCigarette smoke miRNA-191 Hepatic insulin resistance Akt IRS-1
Cigarette smoke extract
Type 2 diabetes mellitus
Insulin receptor substrate-1
Protein kinase B;
Fetal bovine serum;
Glyceraldehyde 3-phosphate dehydrogenase;
Quantitative real-time polymerase chain reaction;
Analysis of variance;
Least significant difference
The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA), an experienced, English-speaking scientific editor for editing.
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.
- American Diabetes A (2004) Diagnosis and classification of diabetes mellitus. Diabetes Care 27(Suppl 1):S5–S10Google Scholar
- 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
- 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
- Li P et al (2016) Hematopoietic-derived galectin-3 causes cellular and systemic insulin resistance. Cell 167(973–984):e12Google Scholar
- 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
- 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
- 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
- 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
- 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