Cover Story Current Issue

Obesity represents a complex medical and behavioural problem which is insufficiently managed by current treatment interventions. Over the past decades, it has become increasing clear that the brain plays a fundamental role in regulating energy balance and body weight homeostasis. Central control of eating and energy balance is determined by a rich interplay of humoral, neuronal and molecular mechanisms.

Henrik H. Hansen, Johanna Perens, Urmas Roostalu, Jacob Lercke Skytte, ... Jacob Hecksher-Sørensen

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Current Issue

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

Nina Sonne, Morten A. Karsdal, Kim Henriksen

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.

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

Nina Sonne, Morten A. Karsdal, Kim Henriksen

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.

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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The 8th Helmholtz Diabetes Conference

The 8th Helmholtz Diabetes Conference will take place virtually from May 10th-12th. This year, the conference will focus on the genetic and epigenetic mechanisms involved in the development of diabetes.

For more information and to register, click here.