Skip to main content
SpringerLink
Log in

Impaired cell surface expression of GLP1R variants determines T2D and obesity risk in humans

  • Research Briefing
  • Published:

From Nature Metabolism

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Selection process and functional profiling of GLP1R variants.

References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42255-023-00888-7

  • Springer Nature Limited

Search

Navigation