Theranostics 2021; 11(16):7829-7843. doi:10.7150/thno.46882 This issue Cite

Research Paper

MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase

Hui Zheng1,2 *, Jian Wan3*, Yi Shan4 *, Xi Song3, Jie Jin5, Qing Su5, Song Chen3, Xinyuan Lu3, Jialin Yang2, Quanmin Li1, Yuping Song2✉, Bo Li5✉

1. Medical College of Soochow University, Suzhou, Jiangsu; PLA Rocket Force Characteristic Medical Center, Beijing, China.
2. Department of Endocrinology and Metabolic Diseases, Minhang Hospital, Fudan University, Shanghai 201100, China.
3. Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, China.
4. Department of Emergency and ICU, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
5. Department of Endocrinology and Metabolic Diseases, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
* Hui Zheng, Jian Wan and Yi Shan contributed equally to this work.

Citation:
Zheng H, Wan J, Shan Y, Song X, Jin J, Su Q, Chen S, Lu X, Yang J, Li Q, Song Y, Li B. MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase. Theranostics 2021; 11(16):7829-7843. doi:10.7150/thno.46882. https://www.thno.org/v11p7829.htm
Other styles

File import instruction

Abstract

Graphic abstract

Aims/hypothesis: MicroRNAs (miRNAs) are known to contribute to many metabolic diseases, including type 2 diabetes. This study aimed to investigate the roles and molecular mechanisms of miR-185-5p in the regulation of hepatic gluconeogenesis.

Methods: MicroRNA high-throughput sequencing was performed to identify differentially expressed miRNAs. High-fat diet-induced obese C57BL/6 mice and db/db mice, a genetic mouse model for diabetes, were used for examining the regulation of hepatic gluconeogenesis. Quantitative reverse transcriptase PCR and Western blotting were performed to measure the expression levels of various genes and proteins. Luciferase reporter assays were used to determine the regulatory roles of miR-185-5p on G6Pase expression.

Results: Hepatic miR-185-5p expression was significantly decreased during fasting or insulin resistance. Locked nucleic acid (LNA)-mediated suppression of miR-185-5p increased blood glucose and hepatic gluconeogenesis in healthy mice. In contrast, overexpression of miR-185-5p in db/db mice alleviated blood hyperglycemia and decreased gluconeogenesis. At the molecular level, miR-185-5p directly inhibited G6Pase expression by targeting its 3'-untranslated regions. Furthermore, metformin, an anti-diabetic drug, could upregulate miR-185-5p expression to suppress G6Pase, leading to hepatic gluconeogenesis inhibition.

Conclusions/interpretation: Our findings provided a novel insight into the role of miR-185-5p that suppressed hepatic gluconeogenesis and alleviated hyperglycemia by targeting G6Pase. We further identified that the /G6Pase axis mediated the inhibitory effect of metformin on hepatic gluconeogenesis. Thus, miR-185-5p might be a therapeutic target for hepatic glucose overproduction and fasting hyperglycemia.

Keywords: Type 2 diabetes, hyperglycemia, hepatic gluconeogenesis, miR-185-5p, metformin


Citation styles

APA
Zheng, H., Wan, J., Shan, Y., Song, X., Jin, J., Su, Q., Chen, S., Lu, X., Yang, J., Li, Q., Song, Y., Li, B. (2021). MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase. Theranostics, 11(16), 7829-7843. https://doi.org/10.7150/thno.46882.

ACS
Zheng, H.; Wan, J.; Shan, Y.; Song, X.; Jin, J.; Su, Q.; Chen, S.; Lu, X.; Yang, J.; Li, Q.; Song, Y.; Li, B. MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase. Theranostics 2021, 11 (16), 7829-7843. DOI: 10.7150/thno.46882.

NLM
Zheng H, Wan J, Shan Y, Song X, Jin J, Su Q, Chen S, Lu X, Yang J, Li Q, Song Y, Li B. MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase. Theranostics 2021; 11(16):7829-7843. doi:10.7150/thno.46882. https://www.thno.org/v11p7829.htm

CSE
Zheng H, Wan J, Shan Y, Song X, Jin J, Su Q, Chen S, Lu X, Yang J, Li Q, Song Y, Li B. 2021. MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase. Theranostics. 11(16):7829-7843.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image