METTL3 is required for maintaining β-cell function

Area of Science:

• Molecular Biology
• Endocrinology
• Metabolic Diseases

Background:

• N6-methyladenosine (m⁶A) mRNA methylation is implicated in obesity and type 2 diabetes.
• The role of METTL3, the primary m⁶A methyltransferase, in pancreatic β-cell function during diabetes remains unclear.

Purpose of the Study:

• To investigate the role of METTL3 in regulating pancreatic β-cell function and failure in the context of diabetes.

Main Methods:

• Examined METTL3 expression under inflammatory and oxidative stress conditions.
• Generated islet β-cell-specific Mettl3 knockout mice.
• Assessed β-cell function, glucose homeostasis, and expression of insulin secretion-related genes.

Main Results:

• METTL3 expression is reduced under inflammatory and oxidative stress.
• Islet β-cell-specific deletion of Mettl3 leads to β-cell failure and hyperglycemia.
• Reduced m⁶A modification and decreased expression of insulin secretion genes were observed in Mettl3-deficient β-cells.

Conclusions:

• METTL3 plays a critical role in maintaining β-cell function and preventing hyperglycemia.
• METTL3 downregulation contributes to β-cell failure in diabetes.
• METTL3 represents a potential therapeutic target for treating diabetes-associated β-cell dysfunction.