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Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart

Overview of attention for article published in Cardiovascular Diabetology, May 2023
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Title
Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart
Published in
Cardiovascular Diabetology, May 2023
DOI 10.1186/s12933-023-01859-8
Pubmed ID
Authors

Ramón Aranda-Domene, Esteban Orenes-Piñero, José María Arribas-Leal, Sergio Canovas-Lopez, Jesús Hernández-Cascales

Abstract

Glucagon is thought to increase heart rate and contractility by stimulating glucagon receptors and increasing 3',5'-cyclic adenosine monophosphate (cAMP) production in the myocardium. This has been confirmed in animal studies but not in the human heart. The cardiostimulatory effects of glucagon have been correlated with the degree of cardiac dysfunction, as well as with the enzymatic activity of phosphodiesterase (PDE), which hydrolyses cAMP. In this study, the presence of glucagon receptors in the human heart and the inotropic and chronotropic effects of glucagon in samples of failing and nonfailing (NF) human hearts were investigated. Concentration‒response curves for glucagon in the absence and presence of the PDE inhibitor IBMX were performed on samples obtained from the right (RA) and left atria (LA), the right (RV) and left ventricles (LV), and the sinoatrial nodes (SNs) of failing and NF human hearts. The expression of glucagon receptors was also investigated. Furthermore, the inotropic and chronotropic effects of glucagon were examined in rat hearts. In tissues obtained from failing and NF human hearts, glucagon did not exert inotropic or chronotropic effects in the absence or presence of IBMX. IBMX (30 µM) induced a marked increase in contractility in NF hearts (RA: 83 ± 28% (n = 5), LA: 80 ± 20% (n = 5), RV: 75 ± 12% (n = 5), and LV: 40 ± 8% (n = 5), weaker inotropic responses in the ventricular myocardium of failing hearts (RV: 25 ± 10% (n = 5) and LV: 10 ± 5% (n = 5) and no inotropic responses in the atrial myocardium of failing hearts. IBMX (30 µM) increased the SN rate in failing and NF human hearts (27.4 ± 3.0 beats min-1, n = 10). In rat hearts, glucagon induced contractile and chronotropic responses, but only contractility was enhanced by 30 µM IBMX (maximal inotropic effect of glucagon 40 ± 8% vs. 75 ± 10%, in the absence or presence of IBMX, n = 5, P < 0.05; maximal chronotropic response 77.7 ± 6.4 beats min-1 vs. 73 ± 11 beats min-1, in the absence or presence of IBMX, n = 5, P > 0.05). Glucagon receptors were not detected in the human heart samples. Our results conflict with the view that glucagon induces inotropic and chronotropic effects and that glucagon receptors are expressed in the human heart.

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Mendeley readers

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The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 2 40%
Other 1 20%
Researcher 1 20%
Unspecified 1 20%
Readers by discipline Count As %
Unspecified 2 40%
Materials Science 1 20%
Unknown 2 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 June 2023.
All research outputs
#18,643,036
of 23,926,844 outputs
Outputs from Cardiovascular Diabetology
#1,063
of 1,454 outputs
Outputs of similar age
#132,136
of 206,809 outputs
Outputs of similar age from Cardiovascular Diabetology
#20
of 26 outputs
Altmetric has tracked 23,926,844 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,454 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.5. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 206,809 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.