Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart
Abstract Background 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 effe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-023-01859-8 |
| _version_ | 1797811936830685184 |
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| author | Ramón Aranda-Domene Esteban Orenes-Piñero José María Arribas-Leal Sergio Canovas-Lopez Jesús Hernández-Cascales |
| author_facet | Ramón Aranda-Domene Esteban Orenes-Piñero José María Arribas-Leal Sergio Canovas-Lopez Jesús Hernández-Cascales |
| author_sort | Ramón Aranda-Domene |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions Our results conflict with the view that glucagon induces inotropic and chronotropic effects and that glucagon receptors are expressed in the human heart. |
| first_indexed | 2024-03-13T07:31:07Z |
| format | Article |
| id | doaj.art-0828f01fdbdd4845bce98e15da89ead2 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-13T07:31:07Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-0828f01fdbdd4845bce98e15da89ead22023-06-04T11:05:45ZengBMCCardiovascular Diabetology1475-28402023-05-0122111210.1186/s12933-023-01859-8Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heartRamón Aranda-Domene0Esteban Orenes-Piñero1José María Arribas-Leal2Sergio Canovas-Lopez3Jesús Hernández-Cascales4Department of Cardiovascular Surgery, Hospital CSV ArrixacaProteomic Unit, Laboratorio Investigación BiosanitariaDepartment of Cardiovascular Surgery, Hospital CSV ArrixacaDepartment of Cardiovascular Surgery, Hospital CSV ArrixacaDepartment of Pharmacology, Faculty Medicine, Edificio LAIB, University of Murcia.Abstract Background 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. Methods 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. Results 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. Conclusions Our results conflict with the view that glucagon induces inotropic and chronotropic effects and that glucagon receptors are expressed in the human heart.https://doi.org/10.1186/s12933-023-01859-8Glucagon receptorHuman heartChronotropismInotropism |
| spellingShingle | Ramón Aranda-Domene Esteban Orenes-Piñero José María Arribas-Leal Sergio Canovas-Lopez Jesús Hernández-Cascales Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart Cardiovascular Diabetology Glucagon receptor Human heart Chronotropism Inotropism |
| title | Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart |
| title_full | Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart |
| title_fullStr | Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart |
| title_full_unstemmed | Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart |
| title_short | Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart |
| title_sort | evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart |
| topic | Glucagon receptor Human heart Chronotropism Inotropism |
| url | https://doi.org/10.1186/s12933-023-01859-8 |
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