Glucagon in Pediatric Metabolic Disorders: Pathophysiology and Therapeutic Perspectives

Over the past century of research, it has become increasingly evident that glucagon should no longer be regarded solely as a counter-regulatory hormone to insulin. Its role in the pathophysiology of metabolic disorders-including diabetes, obesity, and non-alcoholic fatty liver disease-appears to be critical. Hyperglucagonemia is a common feature across several metabolic conditions, not only in adults but also in pediatric populations, suggesting that glucagon may represent both a pathogenic factor and a potential therapeutic target in metabolic disease. Accordingly, therapeutic strategies have been developed that either inhibit or enhance glucagon activity, depending on the clinical context, and some of these approaches are being applied in pediatric care as well. This review aims to provide a comprehensive overview of the pathophysiological role of glucagon in metabolic diseases, synthesizing recent findings that support novel hypotheses for the management and prevention of these conditions.