Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk to benefit ratio of incretin-based therapies will require completion of long-term cardiovascular outcome studies currently underway in patients with type 2 diabetes mellitus.

中文翻译：

---

肠促胰岛素系统的心血管生物学。

胰高血糖素样肽-1 (GLP-1) 是一种肠促胰岛素激素，可增强葡萄糖刺激的胰岛素分泌并对心血管系统产生直接和间接作用。GLP-1 及其相关的肠促胰岛素激素、葡萄糖依赖性促胰岛素多肽，会被酶二肽基肽酶 4 (DPP-4) 迅速灭活，二肽基肽酶 4 (DPP-4) 是肠促胰岛素生物活性的关键决定因素。两类增强肠促胰岛素作用的药物，GLP-1 受体 (GLP-1R) 激动剂和 DPP-4 抑制剂，用于治疗 2 型糖尿病。我们在此回顾 GLP-1R 激动剂和 DPP-4 抑制剂的心血管生物学，包括对心肌细胞、血管、脂肪细胞、血压控制和餐后脂蛋白分泌的直接和间接影响。GLP-1R 激活和 DPP-4 抑制都在心血管功能障碍的临床前模型中发挥多种心脏保护作用，人类受试者的短期研究似乎证明对缺血性心脏病受试者的心脏功能有适度但有益的作用。在临床前研究中，基于肠促胰岛素的药物可控制体重、改善血糖控制、降低血压、抑制肠道乳糜微粒的分泌并减少炎症。然而，关于这些药物对糖尿病和已确诊心血管疾病患者的心血管作用的信息有限。因此，