The Evolving Role of Glucagon in Metabolic Disease and Beyond

Glucagon, secreted by pancreatic α-cells, plays a crucial role in glucose metabolism through its counter-regulatory effects on insulin. Once regarded solely as a hyperglycemic hormone, glucagon is now recognized as a multifaceted regulator of energy balance, lipid metabolism, thermogenesis, and appetite control. Its dynamic interplay with insulin and other metabolic hormones underscores its central role in maintaining systemic metabolic homeostasis. The recent emergence of dual and triple agonists targeting the glucagon, GLP-1, and GIP receptors has transformed the therapeutic landscape for diabetes and obesity, though debate continues over the optimisation of glucagon pathways for metabolic benefit.This Research Topic aims to deepen understanding of glucagon’s evolving physiological and therapeutic roles in metabolic regulation. We welcome original research, reviews, and perspectives that explore the molecular mechanisms underlying glucagon action, the biology of the glucagon receptor, and translational approaches for glucagon-based therapeutics. By integrating mechanistic and clinical insights, this collection seeks to clarify glucagon’s dualistic role in health and disease, and to evaluate its potential as a target for next-generation interventions in metabolic disorders. Submissions of interest include, but are not limited to:• Mechanistic insights into glucagon and glucose homeostasis• Glucagon receptor biology and signaling regulation• Integration of glucagon, GLP-1, and GIP receptor activity in metabolic therapy• Roles of glucagon in lipid metabolism, thermogenesis• The role of glucagon in liver-pancreatic islet-adipose tissue axis• Glucagon’s action in the central nervous system (e.g appetite control)• Controversies and challenges in glucagon-targeted interventions• Translational and clinical advances in glucagon-based therapeuticsTwo editors in this collection are employed by Eli Lilly and Company, which is a pharmaceutical company. All editorial decisions will be made in accordance with Frontiers’ policies, ensuring an independent and unbiased review process. Topic editors: Tamer Coskun, Roger Chen, Alejandra Tomas Catala, Kirk M. Habegger, William Roell Source: https://www.frontiersin.org/research-topics/76177/the-evolving-role-of-glucagon-in-metabolic-disease-and-beyond