What question did this study set out to answer?

To investigate the role of endoplasmic reticulum-mitochondria contact sites in GLP-1 secretion from L cells in the gut, especially under conditions of obesity and type 2 diabetes.

March 10, 2026Diabetologia0 citationsOpen Access

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

AHAlexandre Humbert MNMargaux Nawrot NBNadia Bendridi

Key Points

To investigate the role of endoplasmic reticulum-mitochondria contact sites in GLP-1 secretion from L cells in the gut, especially under conditions of obesity and type 2 diabetes.
Analyzed calcium coupling between endoplasmic reticulum and mitochondria in gut L cells
Examined glucose-induced GLP-1 secretion
Compared effects in normal versus obese and type 2 diabetes models
Identified impaired GLP-1 secretion in L cells during obesity and type 2 diabetes
Demonstrated a novel role for calcium coupling in nutrient sensing
Reinforced the potential of targeting mitochondria-associated membranes to improve glycemic control

Abstract

These results point to a new role for ER-mitochondria calcium coupling in glucose-induced GLP-1 secretion in L cells of the gut, which is impaired in obesity and type 2 diabetes, providing a novel target for the modulation of GLP-1 secretion. Therefore, these data reinforce the potential targeting of MAMs to improve glycaemic outcomes in metabolic diseases.

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