Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Downregulation of miR-34a represses insulin resistance and mediates glucose metabolism by upregulating IGF2 to activate PI3K/AKT signaling pathway

Bohuan Duan¹, Yanjun Wang², Jiwen Liao³, Aizatiguli Kadeer⁴, Jia Wang¹, Palidan Wubuer⁵

¹Department of Internal Medicine, Urumqi International Hospital,; ²Department of Emergency, Urumqi International Hospital; ³Department of Surgery, Urumqi International Hospital; ⁴Department of Science and Education Section, Urumqi International Hospital; ⁵Department of Internal Medicine, Urumqi Hospital of Traditional Chinese Medicine, Urumqi City, Xinjiang Uygur Autonomous Region 830001, China.

For correspondence:- Palidan Wubuer Email: palidan9025@163.com Tel:+869914508275

Accepted: 25 November 2021 Published: 30 December 2021

Citation: Duan B, Wang Y, Liao J, Kadeer A, Wang J, Wubuer P. Downregulation of miR-34a represses insulin resistance and mediates glucose metabolism by upregulating IGF2 to activate PI3K/AKT signaling pathway. Trop J Pharm Res 2021; 20(12):2481-2487 doi: 10.4314/tjpr.v20i12.4

© 2021 The authors.
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Abstract

Purpose: To investigate the effects of miR-34a on insulin resistance and glucose metabolism in type 2 diabetes.

Methods: Human hepatocarcinoma (HepG2) cells were incubated with palmitic acid (PA) for the establishment of a cell model of insulin resistance. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), while insulin resistance was evaluated by glucose consumption. expressions of miR-34a and glucose transporter 4 were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR), while western blotting was used to determine protein expressions of glucose transporter 4 and proteins involved in the downstream pathway. Glucose uptake was assessed by flow cytometry whereas the target gene of miR-34a was determined using a luciferase activity assay.

Results: PA treatment induced a decrease in cell viability in HepG2 cells, and promoted glucose production and miR-34a expression. Silencing of miR-34a conferred insulin sensitivity on PA-treated HepG2 cells. Palmitic acid treatment also reduced insulin-induced NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose] uptake in HepG2 cells, while knockdown of miR-34a attenuated a PA-induced decrease of 2-NBDG uptake in insulin-induced HepG2 cells. Knockdown of miR-34a promoted mRNA and protein expression of glucose transporter 4 in PA and insulin-induced HepG2 cells. MiRNA-34a directly bound to the 3´-UTR of insulin-like growth factor 2 (IGF2), and silencing of miR-34a attenuated the PA-induced decrease in IGF2 expression in HepG2 cells. Interference of miR-34a attenuated IGF2 silencing of the induced decrease in IGF2, glucose transporter 4, and AKT phosphorylation in PA-treated HepG2 cells.

Conclusion: Downregulation of miR-34a promotes glucose consumption and represses insulin resistance by upregulating IGF2 to activate AKT pathway, thus providing a potential target for the treatment of type 2 diabetes.

Keywords: MiR-34a, Insulin-like growth factor 2, Insulin resistance, Glucose metabolism