Endoplasmic reticulum–mitochondria contact sites are signalling hubs connecting nutrient sensing and GLP-1 secretion in L cells of the mouse gut: from physiology to obesity and type 2 diabetes – published online 08/03/2026

Alexandre Humbert, Margaux Nawrot, Nadia Bendridi, Yves Gouriou, Nicolas Bertocchini, Marie‑Agnès Chauvin, Jingwei Ji‑Cao, Christine Durand, Aurélie Vieille‑Marchiset, Claudie Pinteur, Béatrice Morio, Frank Reimann, Bruno Guerci, Magalie A. Ravier, Sophie Lestavel, Jennifer Rieusset

Glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L cells after nutrient ingestion and plays a key role in regulating glucose levels and satiety in humans. Many current therapeutics for type 2 diabetes aim to increase circulating GLP-1 levels; however, to develop more effective treatment strategies, the identification of new molecular mechanisms of nutrient-induced GLP-1 secretion by enteroendocrine L cells is required. In this issue, Humbert and Nawrot et al (https://doi.org/10.1007/s00125-026-06693-7) present findings from a mechanistic study using different models of enteroendocrine L cells (in vitro, ex vivo and in vivo). They identify a new role for endoplasmic reticulum (ER)–mitochondria calcium coupling in nutrient-induced GLP-1 secretion; this is lost in obese mice, resulting in lower GLP-1 release. The authors conclude that these findings reinforce the potential of targeting ER–mitochondria contact sites to improve glycaemic outcomes in metabolic diseases.