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