Mono and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases.
Animals
Calcitonin
/ agonists
Calcitonin Gene-Related Peptide
/ pharmacology
Humans
Insulin Resistance
Islet Amyloid Polypeptide
/ agonists
Metabolic Diseases
/ drug therapy
Obesity
/ drug therapy
Receptors, Calcitonin
/ agonists
Receptors, Calcitonin Gene-Related Peptide
/ agonists
Receptors, Cell Surface
/ drug effects
Weight Loss
Amylin
CGRP
DACRA
Diabetes
Insulin sensitivity
Obesity
Pharmacology
Preclinical
Receptors
Treatments
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
31
08
2020
revised:
28
10
2020
accepted:
29
10
2020
pubmed:
10
11
2020
medline:
20
11
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
SCOPE OF REVIEW
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.
MAJOR CONCLUSIONS
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.
Identifiants
pubmed: 33166741
pii: S2212-8778(20)30183-6
doi: 10.1016/j.molmet.2020.101109
pmc: PMC8085567
pii:
doi:
Substances chimiques
Islet Amyloid Polypeptide
0
Receptors, Calcitonin
0
Receptors, Calcitonin Gene-Related Peptide
0
Receptors, Cell Surface
0
Calcitonin
9007-12-9
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
101109Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.
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