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胰淀素、降钙素和 CGRP 受体的单激动剂和双激动剂及其在代谢性疾病中的潜在作用。

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

机构信息

Nordic Bioscience Biomarkers and Research, Herlev, Denmark.

Nordic Bioscience Biomarkers and Research, Herlev, Denmark; KeyBioscience AG, Stans, Switzerland.

出版信息

Mol Metab. 2021 Apr;46:101109. doi: 10.1016/j.molmet.2020.101109. Epub 2020 Nov 7.

DOI:10.1016/j.molmet.2020.101109
PMID:33166741
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8085567/
Abstract

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.

摘要

背景

代谢性疾病的治疗方法众多，但要提高超出减肥诱导的胰岛素敏感性仍然具有挑战性。因此，人们仍在继续寻找新的治疗候选药物，这些药物可以在结合现有治疗方案的基础上刺激胰岛素敏感性并增加减肥效果。降钙素基因相关肽（CGRP）和胰淀素属于同一肽家族，已被探索用于治疗代谢性疾病。然而，它们的全部潜力仍存在争议。

综述范围

本文介绍了这个相当复杂的肽家族及其相应的受体。我们讨论了这些肽的生理学，重点是代谢和胰岛素敏感性。我们还全面回顾了胰淀素、降钙素、CGRP 和肽衍生物作为代谢性疾病治疗药物的药理学潜力，强调了它们基于临床前和临床研究增加胰岛素敏感性的能力。

主要结论

胰淀素受体激动剂和双重胰淀素和降钙素受体激动剂是相关的治疗候选药物，尤其是因为它们在增加胰岛素敏感性的同时还能辅助减肥，其独特的作用模式补充了基于肠促胰岛素的治疗方法。然而，CGRP 及其衍生物似乎对代谢仅有适度影响，如果有的话，并且不再被视为代谢性疾病的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/49152626f652/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/490b42888eac/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/c0923c3ea337/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/9c6a02854e13/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/caa99b180640/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/8ee0acd67f3e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/49152626f652/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/490b42888eac/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/c0923c3ea337/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/9c6a02854e13/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/caa99b180640/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/8ee0acd67f3e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcbf/8085567/49152626f652/gr6.jpg

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