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Mono and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases.

Authors
  • Sonne, Nina1
  • Karsdal, Morten A2
  • Henriksen, Kim3
  • 1 Nordic Bioscience Biomarkers and Research, Herlev, Denmark. , (Denmark)
  • 2 Nordic Bioscience Biomarkers and Research, Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. , (Switzerland)
  • 3 Nordic Bioscience Biomarkers and Research, Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. Electronic address: [email protected] , (Switzerland)
Type
Published Article
Journal
Molecular Metabolism
Publisher
Elsevier BV
Publication Date
Apr 01, 2021
Volume
46
Pages
101109–101109
Identifiers
DOI: 10.1016/j.molmet.2020.101109
PMID: 33166741
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Therapies for metabolic diseases are numerous, yet improving insulin sensitivity beyond that induced by weight loss remains challenging. Therefore, search continues for novel treatment candidates that can stimulate insulin sensitivity and increase weight loss efficacy in combination with current treatment options. Calcitonin gene-related peptide (CGRP) and amylin belong to the same peptide family and have been explored as treatments for metabolic diseases. However, their full potential remains controversial. In this article, we introduce this rather complex peptide family and its corresponding receptors. We discuss the physiology of the peptides with a focus on metabolism and insulin sensitivity. We also thoroughly review the pharmacological potential of amylin, calcitonin, CGRP, and peptide derivatives as treatments for metabolic diseases, emphasizing their ability to increase insulin sensitivity based on preclinical and clinical studies. Amylin receptor agonists and dual amylin and calcitonin receptor agonists are relevant treatment candidates, especially because they increase insulin sensitivity while also assisting weight loss, and their unique mode of action complements incretin-based therapies. However, CGRP and its derivatives seem to have only modest if any metabolic effects and are no longer of interest as therapies for metabolic diseases. Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.

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