Gcg, the preproglucagon gene, is expressed in specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and certain neurons in the nucleus of the solitary tract. It encodes multiple peptides such as glucagon, glucagon-like peptide-1 (GLP-1), etc. Glucagon is mainly a counterregulatory hormone for glucose metabolism, increasing glucose production when blood glucose levels are threatened. GLP-1 improves glucose homeostasis by stimulating insulin release and reducing glucagon secretion [1].

In GcgGut-/-mice with genetic reduction of Gcg expression throughout the small and large bowel, the acute GLP-1 response to olive oil or arginine administration was markedly diminished, indicating the importance of Gcg in the acute L cell response to these secretagogues. In GcgDistalGut-/-mice with selective reduction of Gcg expression in the distal gut, the increase in plasma GLP-1 levels following the administration of some agonists like GPR119 agonist AR231453 or melanocortin-4 receptor agonist LY2112688 was markedly diminished, revealing the role of distal gut Gcg in the GLP-1 response to these agonists [2].

In conclusion, Gcg is crucial for glucose and energy homeostasis through the peptides it encodes. The study of Gcg knockout mouse models, such as GcgGut-/-and GcgDistalGut-/ -, has provided insights into its role in GLP-1 secretion in response to various stimuli, contributing to our understanding of glucose metabolism-related biological processes and potentially related disease mechanisms [1,2].