摘要
糖尿病肾病是导致西方社会终末期肾病的主要原因。至目前为止,中断的肾素-血管紧张素系统是最有效的糖尿病肾病干预系统,但是这些药物治疗疾病时进展缓慢。因此,寻求一个新的治疗靶点十分重要。晚期糖化终产物受体(RAGE)异常活化通过结合多种配体和导致活性氧(ROS)、炎症和纤维化的生成而与糖尿病肾病的发病机制有关。在最近几年,在发展有效的RAGE拮抗剂方面,科学家已经做出了巨大的努力,然而,直接以RAGE为靶点可能并不科学。胰高血糖素样肽-1(GLP-1)由小肠L细胞产生,并能介导葡萄糖依赖性胰岛素的释放。基于肠促胰岛素治疗,GLP-1受体激动剂和dipeptidylpeptidase-4(DPP4)抑制剂是一种新型用于治疗2型糖尿病的降糖药物。然而,GLP-1胰腺外功能如抗凋亡和抗炎的特性越来越受到人的重视。在糖尿病动物模型中,基于肠促胰素的治疗方法具有肾脏保护作用。有趣的是,GLP-1能干扰信号传导和RAGE的表达。本文旨在于讨论RAGE和促胰岛素通路的相互作用、GLP-1 /肠促胰岛素通路在DN的效用。通过GLP-1激动间接以RAGE为靶治疗糖尿病肾病患者是可行的。
关键词: 糖尿病肾病,dipeptidylpeptidase-4(DPP4)、胰高血糖素样肽-1,肠,肾,晚期糖基化终产物受体。
Current Drug Targets
Title:Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?
Volume: 17 Issue: 11
Author(s): Karly C. Sourris, Henry Yao, George Jerums, Mark E.Cooper, Elif I. Ekinci, Melinda T. Coughlan
Affiliation:
关键词: 糖尿病肾病,dipeptidylpeptidase-4(DPP4)、胰高血糖素样肽-1,肠,肾,晚期糖基化终产物受体。
摘要: Diabetic nephropathy is the major cause of end-stage renal disease in Western societies. To date, interruption of the Renin-Angiotensin System is the most effective intervention for diabetic nephropathy, however these agents only slow progression of the disease. Thus, there is a major unmet need for new therapeutic targets. Aberrant activation of the receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic nephropathy via binding to a variety of ligands and inciting reactive oxygen species (ROS) production, inflammation and fibrosis. In recent years there have been considerable efforts in the development of effective RAGE antagonists, however, direct RAGE targeting may be problematic. Glucagon like peptide-1 (GLP-1) is an incretin hormone released by the L-cells of the small intestine to mediate glucose-dependent insulin release from pancreatic islets. The incretin-based therapies, GLP-1 receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors, are novel glucose-lowering agents used in type 2 diabetes. However, the extra pancreatic functions of GLP-1 have gained attention, including putative anti-apoptotic and anti-inflammatory properties. In rodent models of diabetes, incretin-based therapies are renoprotective. Interestingly, GLP-1 has been shown to interfere with the signalling and expression of RAGE. The current review aims to give an overview of the interactions between the RAGE and incretin pathways and to discuss the utility of targeting the GLP-1/incretin pathway in DN. It is possible that indirect targeting of RAGE through GLP-1 agonism will be of clinical benefit to patients with diabetic nephropathy.
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Karly C. Sourris, Henry Yao, George Jerums, Mark E.Cooper, Elif I. Ekinci, Melinda T. Coughlan , Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?, Current Drug Targets 2016; 17 (11) . https://dx.doi.org/10.2174/1389450116666150722141418
DOI https://dx.doi.org/10.2174/1389450116666150722141418 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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