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Metabolism

New insights into the regulation of GIPR signalling

Nature Reviews Endocrinology volume 20, pages 571–572 (2024)Cite this article

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Two recent studies have unravelled novel modes of glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling regulation. Kizilkaya et al. characterized the effect of changes in β-arrestin 2 coupling with naturally occurring GIPR coding variants, whereas Regmi et al. investigated GIPR expression profiles and functional regulation in adipocytes.

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References

  1. Heise, T. et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diabetes Care 46, 998–1004 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Véniant, M. M. et al. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat. Metab. 6, 290–303 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kizilkaya, H. S. et al. Loss of function glucose-dependent insulinotropic polypeptide receptor variants are associated with alterations in BMI, bone strength and cardiovascular outcomes. Front. Cell Dev. Biol. 9, 749607 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kizilkaya, H. S. et al. Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes. Nat. Metab. 6, 1268–1281 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Manchanda, Y. et al. Enhanced endosomal signaling and desensitization of GLP-1R vs GIPR in pancreatic beta cells. Endocrinology 164, bqad028 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Manchanda, Y. et al. Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling. Sci. Signal. 17, eabq7038 (2024).

    Article  PubMed  Google Scholar 

  7. Bitsi, S. et al. Divergent acute versus prolonged pharmacological GLP-1R responses in adult β cell-specific β-arrestin 2 knockout mice. Sci. Adv. 9, eadf7737 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Killion, E. A. et al. Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism. Nat. Commun. 11, 4981 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Regmi, A. et al. Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor. Cell Metab. 36, 1534–1549.e7 (2024).

    Article  CAS  PubMed  Google Scholar 

  10. Campbell, J. E. et al. GIPR is predominantly localized to nonadipocyte cell types within white adipose tissue. Diabetes 71, 1115–1127 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK

    Yusman Manchanda & Alejandra Tomas

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  1. Yusman Manchanda
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  2. Alejandra Tomas
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Correspondence to Alejandra Tomas.

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The authors declare no competing interests.

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Manchanda, Y., Tomas, A. New insights into the regulation of GIPR signalling. Nat Rev Endocrinol 20, 571–572 (2024). https://doi.org/10.1038/s41574-024-01027-2

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