Incretin-mediated control of cardiac energy metabolism

in Journal of Endocrinology
Authors:
Jordan S F Chan Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada

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https://orcid.org/0009-0006-1567-8772
,
Tanin Shafaati Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada

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, and
John R Ussher Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada

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https://orcid.org/0000-0001-9574-5707

Correspondence should be addressed to J R Ussher: jussher@ualberta.ca

This paper forms part of a special collection on Incretins. The guest editors for this collection were Timo D Müller and Erin Mulvihill.

DOI:
https://doi.org/10.1530/JOE-24-0011
Volume/Issue:
Volume 263: Issue 1
Article Type:
Review Article
Article ID:
e240011
Online Publication Date:
08 Aug 2024
Copyright:
© the author(s) 2024
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Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) are incretin hormones that stimulate insulin secretion and improve glycemic control in individuals with type 2 diabetes (T2D). Data from several cardiovascular outcome trials for GLP-1 receptor (GLP-1R) agonists have demonstrated significant reductions in the occurrence of major adverse cardiovascular events in individuals with T2D. Although the cardiovascular actions attributed to GLP-1R agonism have been extensively studied, little is known regarding the cardiovascular consequences attributed to GIP receptor (GIPR) agonism. As there is now an increasing focus on the development of incretin-based co-agonist therapies that activate both the GLP-1R and GIPR, it is imperative that we understand the mechanism(s) through which these incretins impact cardiovascular function. This is especially important considering that cardiovascular disease represents the leading cause of death in individuals with T2D. With increasing evidence that perturbations in cardiac energy metabolism are a major contributor to the pathology of diabetes-related cardiovascular disease, this may represent a key component through which GLP-1R and GIPR agonism influence cardiovascular outcomes. Not only do GIP and GLP-1 increase the secretion of insulin, they may also modify glucagon secretion, both of which have potent actions on cardiac substrate utilization. Herein we will discuss the potential direct and indirect actions through which GLP-1R and GIPR agonism impact cardiac energy metabolism while interrogating the evidence to support whether such actions may account for incretin-mediated cardioprotection in T2D.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2024
Article ID:
e240011
Article Type:
Review Article
Received Date:
15 Jan 2024
Accepted Date:
16 Jul 2024
Print Publication Date:
01 Oct 2024
Online Publication Date:
08 Aug 2024
Keywords:
cardiac energy metabolism; cardiovascular disease; glucose-dependent insulinotropic polypeptide; glucose-dependent insulinotropic polypeptide receptor; glucagon-like peptide 1; glucagon-like peptide-1 receptor; incretins

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