Summary
Published in Science Translational Medicine (2025), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Bahl, Varun, et al. G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells
G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells
Research Overview
Elevated glucagon is a feature of type 2 diabetes, and α cell-intrinsic mechanisms are known to regulate its secretion. This study focused on G6PC2, whose enzyme opposes glucokinase and whose genetic variants are reproducibly associated with fasting blood glucose and hemoglobin A1c.
The authors found that trait-associated variants in the G6PC2 promoter sit in open chromatin in α cells as well as β cells, documented allele-specific G6PC2 expression in human α cells, and used α cell-specific gene ablation in mice to show that G6PC2 plays a critical role in controlling glucagon secretion.
Key Discoveries
- G6PC2 promoter variants located in open chromatin in α cells, not only β cells
- Allele-specific G6PC2 expression documented in human α cells
- α cell-specific ablation in mice established G6PC2's role in glucagon control
