Glucagon and Its Receptors in the Mammalian Heart

Abstract

Glucagon exerts effects on the mammalian heart. These effects include alterations in the force of contraction, beating rate, and changes in the cardiac conduction system axis. The cardiac effects of glucagon vary according to species, region, age, and concomitant disease. Depending on the species and region studied, the contractile effects of glucagon can be robust, modest, or even absent. Glucagon is detected in the mammalian heart and might act with an autocrine or paracrine effect on the cardiac glucagon receptors. The glucagon levels in the blood and glucagon receptor levels in the heart can change with disease or simultaneous drug application. Glucagon might signal via the glucagon receptors but, albeit less potently, glucagon might also signal via glucagon-like-peptide-1-receptors (GLP1-receptors). Glucagon receptors signal in a species- and region-dependent fashion. Small molecules or antibodies act as antagonists to glucagon receptors, which may become an additional treatment option for diabetes mellitus. Hence, a novel review of the role of glucagon and the glucagon receptors in the mammalian heart, with an eye on the mouse and human heart, appears relevant. Mouse hearts are addressed here because they can be easily genetically modified to generate mice that may serve as models for better studying the human glucagon receptor.

Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet inDrosophila

“…However, evidence of GCGR expression in human heart tissue has been conflicting. No cardiac signal was detected when using radioactively labeled glucagon (Bomholt et al, 2022), results of mRNA data have been inconsistent (Aranda-Domene et al, 2023; Bomholt et al, 2022), and protein data for GCGR to support cardiac expression is lacking (Neumann et al, 2023). Here, we identified an endocrine neuron-heart axis using a fly model for high-fat diet-induced arrhythmia.…”

“…Glucagon has been repeatedly shown to affect heart contraction and heart rate. However, the nature of this effect is complex; whether glucagon acts anti-or pro-arrhythmogenic seems to depend on context, such as a non-failing heart or a heart at acute or chronic failure (Neumann et al, 2023). That said, glucagon-producing tumors, i.e., glucagonomas, can cause tachycardia (a form of arrhythmia defined as >100 heart beats per minute) and heart failure without secondary cause (Chang-Chretien et al, 2004;Zhang et al, 2014).…”

“…Glucagon has been repeatedly shown to affect heart contraction and heart rate. However, the nature of this effect is complex; whether glucagon acts anti- or pro-arrhythmogenic seems to depend on context, such as a non-failing heart or a heart at acute or chronic failure (Neumann et al, 2023). That said, glucagon-producing tumors, i.e.…”