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二肽基肽酶 4 抑制剂的心血管多效性作用:在理解其额外治疗潜力方面的前沿进展。

Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

机构信息

Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.

出版信息

Cell Signal. 2013 Sep;25(9):1799-803. doi: 10.1016/j.cellsig.2013.05.009. Epub 2013 May 22.

Abstract

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.

摘要

二肽基肽酶 4(DPP-4)是一种广泛表达于多种组织(包括心血管系统)的丝氨酸蛋白酶。在进餐期间,肠内分泌的肠降血糖素,如胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性胰岛素释放肽(GIP)被释放到血管中,这些肠降血糖素具有从胰岛的β细胞释放胰岛素的潜力,从而发挥降血糖作用。然而,这两种肠降血糖素都被 DPP-4 迅速降解。因此,DPP-4 抑制剂可提高 GLP-1 和 GIP 的生物利用度,已被批准用于改善 2 型糖尿病(T2DM)患者的血糖控制。迄今为止,已有五种不同的 DPP-4 抑制剂(通常称为“gliptins”),即西他列汀、维格列汀、沙格列汀、利拉利汀和阿格列汀被批准用于临床。这些药物与饮食和运动一起用于降低糖尿病患者的血糖。T2DM 与心血管疾病风险增加密切相关。越来越多的证据表明,gliptins 除了具有令人信服的抗糖尿病作用外,对心脏和血管还有有益的多效性作用。鉴于 T2DM 患者易患心血管疾病,gliptins 可能在治疗糖尿病心血管并发症方面提供额外的治疗益处。进一步探索 gliptins 的心血管多效潜能可能为这些药物用于 T2DM 和 T2DM 相关危险心血管并发症的双重管理提供新的视角。本文综述了 gliptins 对心血管系统新发现的有益多效性作用。

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