The role of receptor activity-modifying proteins in obesity and diabetes mellitus

in Journal of Molecular Endocrinology
Authors:
Milena A Malcharek Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom

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Abigail Pearce Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom

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Cheryl A Brighton Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom

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David C Hornigold Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom

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Graham Ladds Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom

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https://orcid.org/0000-0001-7320-9612

Correspondence should be addressed to G Ladds: grl30@cam.ac.uk

This paper forms part of a special collection on the theme of GPCRs. The guest editors for this collection were Caroline Gorvin, Aylin Hanyaloglu, and Davide Calebiro.

DOI:
https://doi.org/10.1530/JME-24-0056
Volume/Issue:
Volume 73: Issue 4
Article Type:
Review Article
Article ID:
e240056
Online Publication Date:
30 Oct 2024
Copyright:
© the author(s) 2024
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Receptor activity-modifying proteins (RAMPs) modulate the expression and activity of numerous G protein-coupled receptors, primarily those within class B1. These receptors have important physiological roles, including the regulation of food intake, energy metabolism, and glucose homeostasis. Dysregulation of these pathways can lead to obesity and diabetes mellitus, which present an ever-expanding global challenge. Whilst the roles of class B1 receptors and their peptide agonists in obesity and diabetes have been investigated, the contribution of RAMPs is less well understood. This review summarises the results of RAMP knockout studies, highlighting the involvement of these proteins in the incidence of disease. It then moves to discuss how receptor, RAMP, and agonist expression change in disease states, and the benefits (or detriments) of these agonists to the pathways implicated in disease pathophysiology. Whilst much of the data centres around the calcitonin family of receptors, as their interactions with RAMPs are well established, this review then discusses receptors whose roles in obesity and diabetes are well founded, but the significance of whose interactions with RAMPs is more recently emerging. The conclusion of this study of the literature is, however, that the information surrounding RAMPs is conflicting and multifaceted, and more research is required to fully understand their contribution to obesity and diabetes.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© the author(s) 2024
Article ID:
e240056
Article Type:
Review Article
Received Date:
07 Jun 2024
Accepted Date:
18 Sep 2024
Print Publication Date:
01 Nov 2024
Online Publication Date:
30 Oct 2024
Keywords:
body mass; diabetes; G protein coupled-receptor (GPCR); obesity; receptor activity-modifying protein (RAMP)

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