biostudies-literatureUnknownAustin GNIDDK NIH HHSDiabetes UKWellcome TrustBiotechnology and Biological Sciences Research CouncilGlucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RAs) ameliorate mitochondrial health by increasing mitochondrial turnover in metabolically relevant tissues. Mitochondrial adaptation to metabolic stress is crucial to maintain pancreatic β-cell function and prevent type 2 diabetes (T2D) progression. While the GLP-1R is well-known to stimulate cAMP production leading to Protein Kinase A (PKA) and Exchange Protein Activated by cyclic AMP 2 (Epac2) activation, there is a lack of understanding of the molecular mechanisms linking GLP-1R signalling with mitochondrial and β-cell functional adaptation. Here, we present a comprehensive study in β-cell lines and primary islets that demonstrates that, following GLP-1RA stimulation, GLP-1R-positive endosomes associate with the endoplasmic reticbioRxiv : the preprint server for biology2024.04.28.591531https://www.ebi.ac.uk/biostudies/studies/S-EPMC12338517biostudies-literatureGLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function.PMC12338517227745/Z/23/Z104931/Z/14/Z301619/Z/23/ZUC4 DK098085BB/L015129/119/0006094Bouzakri KGaboriau DCAManchanda YTomas AOqua AICoyle HWithers DJJones BMillership SJZhu MMajorovits EBurgold SLima MGarlick EProkopenko IMuller AAustin GEl Eid LPeres PSolimena MMontoya APoliakova YNixon-Abell JfalseGLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function.Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RAs) ameliorate mitochondrial health by increasing mitochondrial turnover in metabolically relevant tissues. Mitochondrial adaptation to metabolic stress is crucial to maintain pancreatic β-cell function and prevent type 2 diabetes (T2D) progression. While the GLP-1R is well-known to stimulate cAMP production leading to Protein Kinase A (PKA) and Exchange Protein Activated by cyclic AMP 2 (Epac2) activation, there is a lack of understanding of the molecular mechanisms linking GLP-1R signalling with mitochondrial and β-cell functional adaptation. Here, we present a comprehensive study in β-cell lines and primary islets that demonstrates that, following GLP-1RA stimulation, GLP-1R-positive endosomes associate with the endoplasmic retic2025-01-01T00:00:00Z2025 Jul2026-04-08T15:48:22.378Z2026-04-08T05:27:57.258ZS-EPMC123385174079151810.1101/2024.04.28.591531