ORIGINAL ARTICLE

Anti-diabetic effect of hydroxybenzoic acid derivatives in free fatty acid-induced HepG2 cells via miR-1271/IRS1/PI3K/AKT/FOXO1 pathway

Hana Lee

Department of Food Science and Biotechnology, College of Agriculture, Life, & Environmental Sciences, Chungbuk National University, Cheongju, Korea

Contribution: Investigation, Methodology, Writing - original draft

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Junsoo Lee,

Corresponding Author

Junsoo Lee

[email protected]

orcid.org/0000-0001-5557-4229

Department of Food Science and Biotechnology, College of Agriculture, Life, & Environmental Sciences, Chungbuk National University, Cheongju, Korea

Correspondence

Junsoo Lee, Department of Food Science and Biotechnology, College of Agriculture, Life, & Environmental Sciences, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheong-ju, Chungbuk 28644, Korea.

Email: [email protected]

Contribution: Supervision

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Hana Lee,

Hana Lee

Department of Food Science and Biotechnology, College of Agriculture, Life, & Environmental Sciences, Chungbuk National University, Cheongju, Korea

Contribution: Investigation, Methodology, Writing - original draft

Search for more papers by this author

Junsoo Lee,

Corresponding Author

Junsoo Lee

[email protected]

orcid.org/0000-0001-5557-4229

Department of Food Science and Biotechnology, College of Agriculture, Life, & Environmental Sciences, Chungbuk National University, Cheongju, Korea

Correspondence

Email: [email protected]

Contribution: Supervision

Search for more papers by this author

First published: 03 November 2021

https://doi.org/10.1111/jfbc.13993

Citations: 22

Funding information

This research was supported by the Rural Development Administration (grant number: PJ01415004)

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Abstract

Type 2 diabetes is characterized by insulin resistance (IR) and increased hepatic glucose production. MicroRNAs (miRs) are considered regulators of glucose metabolism. This study evaluated anti-diabetic activity of hydroxybenzoic acid derivatives and determined the involvement of miR-1271. Among the hydroxybenzoic acid derivatives, gallic acid (GA) showed the best anti-diabetic activity. GA improved free fatty acid (FFA)-induced hepatic IR, increased glucose consumption, and decreased reactive oxygen species. GA inhibited the upregulation of miR-1271 induced by FFA and upregulated its targets such as p-IRS, p-PI3K, p-AKT, and p-FOXO1, accompanied by the regulation of glucose metabolism genes. The involvement of miR-1271 in the protective effect of GA against IR was further confirmed in the presence of miR-1271 mimic or miR-1271 inhibitor. Our results suggest that GA attenuates IR via the miR-1271/IRS/PI3K/AKT/FOXO1 pathway and thus might be considered for the management of IR.

Practical applications

MicroRNAs can regulate insulin resistance by affecting protein expressions involved in insulin signaling. Experimental data suggest that some phytochemicals regulate the expression of various microRNAs. However, it is not clear whether phenolic acids play any role in the hepatic insulin signaling pathway through the regulation of microRNA expression. This study assessed the anti-diabetic activity of hydroxybenzoic acid derivatives through down-regulation of microRNA-1271 and its association with the IRS1/PI3K/AKT/FOXO1 pathways. This research will be able to offer basic information regarding a potential therapeutic strategy to control hepatic insulin resistance.

CONFLICT OF INTEREST

The authors declared that they have no conflict of interest.

Open Research

DATA AVAILABILITY STATEMENT

All data used to support the findings of this study are included within the article and its supporting information.

Supporting Information

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Anti-diabetic effect of hydroxybenzoic acid derivatives in free fatty acid-induced HepG2 cells via miR-1271/IRS1/PI3K/AKT/FOXO1 pathway

Abstract

Practical applications

CONFLICT OF INTEREST

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

Citing Literature

References

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Anti-diabetic effect of hydroxybenzoic acid derivatives in free fatty acid-induced HepG2 cells via miR-1271/IRS1/PI3K/AKT/FOXO1 pathway

Abstract

Practical applications

CONFLICT OF INTEREST

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

Citing Literature

References

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