METTL3 is required for maintaining β-cell function

Xinzhi Li; Yuze Jiang; Xu Sun; Yongsen Wu; Zheng Chen

doi:10.1016/j.metabol.2021.154702

METTL3 is required for maintaining β-cell function

Metabolism. 2021 Mar:116:154702. doi: 10.1016/j.metabol.2021.154702. Epub 2021 Jan 6.

Authors

Xinzhi Li¹, Yuze Jiang¹, Xu Sun¹, Yongsen Wu¹, Zheng Chen²

Affiliations

¹ HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
² HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. Electronic address: [email protected].

PMID: 33417895
DOI: 10.1016/j.metabol.2021.154702

Abstract

N6-methyladenosine (m⁶A) mRNA methylation has been shown to regulate obesity and type 2 diabetes. However, whether METTL3, the key methyltransferase for m⁶A mRNA methylation, regulates β-cell failure in diabetes has not been fully explored. Here, we show that METTL3 is downregulated under the inflammatory and oxidative stress conditions, and islet β-cell-specific deletion of Mettl3 induces β-cell failure and hyperglycemia, which is likely due to decreased m⁶A modification and reduced expression of insulin secretion-related genes. Overall, METTL3 might be a potential drug target for the treatment of β-cell failure in diabetes.

Keywords: Cell death; Hyperglycemia; Insulin secretion; Islet β cells; METTL3; m(6)A.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus / genetics*
Diabetes Mellitus / pathology
Diabetes Mellitus / physiopathology
Insulin-Secreting Cells / physiology*
Islets of Langerhans / physiology
Islets of Langerhans / physiopathology
Methyltransferases / genetics
Methyltransferases / physiology*
Mice
Mice, Knockout
Pancreatic Diseases / genetics
Pancreatic Diseases / pathology
Pancreatic Diseases / physiopathology

Substances

Methyltransferases
Mettl3 protein, mouse