Different effectiveness of glucagon on the pacemaker activity and contractility in intact dog hearts and in isolated perfused right atria.

Furukawa, Yoshiko; Saegusa, Kimiaki; Ogiwara, Yasuhiro; Chiba, Shigetoshi

doi:10.1536/ihj.27.215

Cited by 6 publications

(10 citation statements)

References 17 publications

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“…Glucagon has an important effect on sino atrial node rate [17] and the antiarrhythmogenic effect of glucagon has been several times reviewed [18–23]. …”

Section: Glucagon Beyond Glucose Metabolismmentioning

confidence: 99%

Glucagon and heart in type 2 diabetes: new perspectives

Ceriello

Genovese

Mannucci

et al. 2016

Cardiovasc Diabetol

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Increased levels of glucagon in type 2 diabetes are well known and, until now, have been considered deleterious. However, glucagon has an important role in the maintenance of both heart and kidney function. Moreover, in the past, glucagon has been therapeutically used for heart failure treatment. The new antidiabetic drugs, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors, are able to decrease and to increase glucagon levels, respectively, while contrasting data have been reported regarding the glucagon like peptide 1 receptors agonists. The cardiovascular outcome trials, requested by the FDA, raised some concerns about the possibility that the dipeptidyl peptidase-4 inhibitors can precipitate the heart failure, while, at least for empagliflozin, a positive effect has been shown in decreasing both cardiovascular death and heart failure. The recent LEADER Trial, showed a significant reduction of cardiovascular death with liraglutide, but a neutral effect on heart failure. A possible explanation of the results with the DPPIV inhibitors and empagliflozin might be related to their divergent effect on glucagon levels. Due to unclear effects of glucagon like peptide 1 receptor agonists on glucagon, the possible role of this hormone in the Leader trial remains unclear.

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“…Glucagon has an important effect on sino atrial node rate [17] and the antiarrhythmogenic effect of glucagon has been several times reviewed [18–23]. …”

Section: Glucagon Beyond Glucose Metabolismmentioning

confidence: 99%

Glucagon and heart in type 2 diabetes: new perspectives

Ceriello

Genovese

Mannucci

et al. 2016

Cardiovasc Diabetol

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“…For example, in the rat heart, glucagon increases contractility in ventricular but not in atrial myocardium [ 5 ]. Despite the lack of inotropic effect in atrial myocardium, glucagon produce a positive chronotropic effect in this tissue [ 7 ]. The reason for this discrepancy was not known but the results of the present study showing a three times higher transcript levels of glucagon receptors in sinoatrial node (the primary cardiac pacemaker), compared to the atrial myocardium, provide a plausible explanation for it.…”

Section: Discusionmentioning

confidence: 99%

“…The positive inotropic effect of glucagon has been established in ventricular myocardium [ 3 – 5 ], but their atrial effects are less well know. Indeed, glucagon seems to be devoid of inotropic effect [ 5 , 6 ] but it produces a positive chronotropic response in atrial myocardium [ 7 ]. The reason behind the differences observed between the atrial inotropic and chronotropic effects of glucagon is unknown but it may result from a different levels of glucagon receptor in atrial myocardium and sino-atrial node.…”

Section: Introductionmentioning

confidence: 99%

Glucagon Increases Beating Rate but Not Contractility in Rat Right Atrium. Comparison with Isoproterenol

2015

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This study evaluated the chronotropic and inotropic responses to glucagon in spontaneously beating isolated right atria of rat heart. For comparison, we also investigated the effects resulting from stimulating β-adrenoceptors with isoproterenol in this tissue. Isoproterenol increased both atrial frequency and contractility but glucagon only enhanced atrial rate. The transcript levels of glucagon receptors were about three times higher in sinoatrial node than in the atrial myocardium. Chronotropic responses to glucagon and isoproterenol were blunted by the funny current (If) inhibitor ZD 7288. Inhibitors of protein kinase A, H-89 and KT-5720 reduced the chronotropic response to glucagon but not to isoproterenol. Inhibition of ryanodine receptors and calcium/calmodulin dependent protein kinase II (important regulators of sarcoplasmic reticulum Ca2+ release), with ruthenium red and KN-62 respectively, failed to alter chronotropic responses of either glucagon or isoproterenol. Non selective inhibition of phosphodiesterase (PDE) with 3-isobutylmethylxantine or selective inhibition of PDE3 or PDE4 with cilostamide or rolipram respectively did not affect chronotropic effects of glucagon or isoproterenol. Our results indicate that glucagon increases beating rate but not contractility in rat right atria which could be a consequence of lower levels of glucagon receptors in atrial myocardium than in sinoatrial node. Chronotropic responses to glucagon or isoproterenol are mediated by If current but not by sarcoplasmic reticulum Ca2+ release, neither are regulated by PDE activity.

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“…Furthermore, glucagon increases contractility in the ventricle, but not in the atrium, of the rat heart [ 11 , 12 ]. In contrast to the differences reported for the inotropic effects of glucagon, its positive chronotropic effect has been consistently obtained in both “in vivo” and “in vitro” studies with isolated atrias obtained from of dog, cat, guinea-pig and rat hearts [ 3 , 6 , 10 ].…”

Section: Animal Studiesmentioning

confidence: 99%

“…The inotropic effects of glucagon seem to be more marked at the ventricular than at the atrial level. For instance, in the dog heart, glucagon produces a robust inotropic effect in ventricular myocardium [ 9 ] but only a slight contractile effect in atrial myocardium [ 10 ]. Furthermore, glucagon increases contractility in the ventricle, but not in the atrium, of the rat heart [ 11 , 12 ].…”

Section: Animal Studiesmentioning

confidence: 99%

Does glucagon have a positive inotropic effect in the human heart?

Hernández-Cascales

2018

Cardiovasc Diabetol

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Glucagon is considered to exert cardiostimulant effects, most notably the enhancement of heart rate and contractility, due to the stimulation of glucagon receptors associated with Gs protein stimulation which causes adenylyl cyclase activation and the consequent increase in 3′,5′-cyclic adenosine monophosphate production in the myocardium. These effects have been extensively demonstrated in experimental studies in different animal species. However, efforts to extrapolate the experimental data to patients with low cardiac output states, such as acute heart failure or cardiogenic shock, have been disappointing. The experimental and clinical data on the cardiac effects of glucagon are described here.

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Different effectiveness of glucagon on the pacemaker activity and contractility in intact dog hearts and in isolated perfused right atria.

Cited by 6 publications

References 17 publications

Glucagon and heart in type 2 diabetes: new perspectives

Glucagon and heart in type 2 diabetes: new perspectives

Glucagon Increases Beating Rate but Not Contractility in Rat Right Atrium. Comparison with Isoproterenol

Does glucagon have a positive inotropic effect in the human heart?

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