Glucagon-like peptide 1 (GLP-1) controls insulin secretion and body weight through activation of its receptor, GLP1R. Large-scale functional analysis of 60 GLP1R genetic variants revealed that loss-of-function (LoF) phenotypes, in particular of cell surface expression, are associated with impaired glucose control and increased adiposity.
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Nauck, M. A., Quast, D. R., Wefers, J. & Meier, J. J. GLP-1 receptor agonists in the treatment of type 2 diabetes — state-of-the-art. Mol. Metab. 46, 101102 (2021). A review that discusses the latest GLP1R-based treatments.
El Eid, L., Reynolds, C. A., Tomas, A. & Jones, B. Biased agonism and polymorphic variation at the GLP-1 receptor: Implications for the development of personalised therapeutics. Pharmacol. Res. 184, 106411 (2022). A review that presents existing GLP1R variants and future therapeutic options.
Bonnefond, A. et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat. Genet. 44, 297–301 (2012). This paper reports a large-scale functional genetics study on rare GPCR variants.
Nogueiras, R., Nauck, M. A. & Tschop, M. H. Gut hormone co-agonists for the treatment of obesity: from bench to bedside. Nat. Metab. 5, 933–944 (2023). A review that presents recent advances in the clinical application of dual and triple GLP1R agonists.
Ulloa-Aguirre, A., Zarinan, T., Gutierrez-Sagal, R. & Tao, Y. X. Targeting trafficking as a therapeutic avenue for misfolded GPCRs leading to endocrine diseases. Front. Endocrinol. (Lausanne) 13, 934685 (2022). A review that presents the state-of-the-art of pharmacological chaperones for GPCRs.
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This is a summary of: Gao, W. et al. Human GLP1R variants affecting GLP1R cell surface expression are associated with impaired glucose control and increased adiposity. Nat. Metab. https://doi.org/10.1038/s42255-023-00889-6 (2023).
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Impaired cell surface expression of GLP1R variants determines T2D and obesity risk in humans. Nat Metab 5, 1654–1655 (2023). https://doi.org/10.1038/s42255-023-00888-7