Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, D-06097 Halle (Saale), Germany.
Department of Cardiac Surgery, Mid-German Heart Center, University Hospital Halle, Ernst Grube Straße 40, D-06097 Halle (Saale), Germany.
Int J Mol Sci. 2023 Aug 15;24(16):12829. doi: 10.3390/ijms241612829.
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.
胰高血糖素对哺乳动物心脏发挥作用。这些作用包括收缩力、跳动频率的改变以及心脏传导系统轴的变化。胰高血糖素对心脏的影响因物种、区域、年龄和伴随疾病而异。根据所研究的物种和区域，胰高血糖素的收缩作用可能很强、适度或甚至不存在。哺乳动物心脏中可检测到胰高血糖素，它可能通过自分泌或旁分泌作用作用于心脏胰高血糖素受体。血液中的胰高血糖素水平和心脏中的胰高血糖素受体水平可能因疾病或同时应用药物而改变。胰高血糖素可能通过胰高血糖素受体发出信号，但尽管作用较弱，胰高血糖素也可能通过胰高血糖素样肽-1 受体 (GLP1 受体) 发出信号。胰高血糖素受体以依赖于物种和区域的方式发出信号。小分子或抗体可作为胰高血糖素受体的拮抗剂，这可能成为治疗糖尿病的另一种选择。因此，对哺乳动物心脏中胰高血糖素和胰高血糖素受体的作用进行新的综述，关注小鼠和人心显得很有必要。本文关注小鼠心脏，因为它们可以很容易地通过基因修饰产生可能有助于更好地研究人类胰高血糖素受体的小鼠模型。
