利拉鲁肽的药理及临床研究进展

 利拉鲁肽是一种酰化胰高血糖素样肽-1（GLP-1）类似物,通过激活GLP-1受体,以葡萄糖依赖性刺激胰岛素分泌并抑制胰高血糖素分泌,临床用于2型糖尿病的二线治疗,可与其他口服降糖药联合使用,但不用于1型糖尿病的治疗。文中通过Medline对利拉鲁肽进行文献检索,并对其药理作用、药动学、临床研究、安全性和药物相互作用等进行综述。     

利拉鲁肽临床研究进展

利拉鲁肽是一种胰高血糖素样肽-1(GLP-1)类似物,通过激活GLP-1受体,以葡萄糖依赖性刺激胰岛素分泌并抑制胰高血糖素分泌,临床用于治疗2型糖尿病。本文综述利拉鲁肽的临床研究进展。     

2型糖尿病治疗药物杜拉鲁肽的研究进展

杜拉鲁肽是一种长效胰高血糖素样肽-1(GLP-1)受体激动剂,能促进胰岛素分泌,保护胰岛β细胞,抑制胰高血糖素分泌,抑制胃排空,降低食欲;临床用于2型糖尿病(T2DM)和肥胖症的治疗;本品不适用于1型糖尿病,也不能替代胰岛素治疗。本文综述了近年来杜拉鲁肽的研究文献,从作用机制、药效学和药动学、临床研究、不良反应等方面介绍GLP-1受体激动剂杜拉鲁肽的研究进展,旨在为临床合理用药提供参考。     

GLP-1R激动剂及正变构调节剂研究进展

胰高血糖素样肽-1受体(glucagon-like peptide-1 receptor, GLP-1R)是治疗2型糖尿病的重要靶标，作为一种G蛋白偶联受体可通过胰高血糖素样肽-1介导胰岛素分泌。该文对胰高血糖素样肽-1和GLP-1R的结构与功能进行综述，并对肽类GLP-1R激动剂、非肽类小分子GLP-1R激动剂和GLP-1R正变构调节剂的设计开发进行讨论，旨在为进一步探寻2型糖尿病的治疗方案提供思路。     

胰高血糖素样肽-1及类似物的降压作用研究进展

胰高血糖素样肽-1是体内一种重要的肠促胰岛素,具有葡萄糖浓度依赖性降糖作用,其类似物已用于2型糖尿病治疗。近年来的临床前和临床研究均发现胰高血糖素样肽-1及类似物有一定程度的降压作用,其作用机制可能与促进水钠排泄、改善血管内皮功能等有关。本文综述胰高血糖素样肽-1及类似物的降压作用。     

胰高血糖素样肽-1受体激动剂药理作用的研究进展

胰高血糖素样肽-1是经胰高血糖素原基因编码、肠道L细胞分泌的多肽类物质,在营养物质、细胞因子、神经信号等刺激下通过促进胰岛素的分泌而发挥降糖作用。近年来,胰高血糖素样肽-1受体激动剂在2型糖尿病治疗方面已获肯定,与传统降糖药物相比,其除可以稳定降糖外,还具有减重、降压、调脂、心血管和肾脏保护等益处。主要对GLP-1受体激动剂药理作用的研究进展进行综述。     

胰高血糖素样肽-1及其对糖尿病的治疗研究进展

胰高血糖素原包含2种胰高血糖素样肽，即胰高血糖素样肽-1(Glucagon-like peptide-1，GUL-1)和胰高血糖素样肽-2(GUL-2)。GLP-1主要是由小肠和大肠的内分泌细胞和脑的神经细胞分泌，通过复杂的机制调节血糖，其中包括对胰岛素和胰高血糖素的分泌、胃的排空及外周胰岛素敏感性的调节，而且可以调节脂肪组织和肌肉的糖原合成，增加胰岛β细胞数量及抑制其凋亡。     

GLP-1改善内质网应激研究进展

胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)主要由肠道L细胞产生和分泌,可以促进胰岛素分泌、抑制胰高血糖素分泌、延缓胃排空及促进胰岛β细胞分化和增殖。内质网应激(endoplasmic reticulum stress,ERS)是2型糖尿病发生发展中重要的环节,近年,GLP-1临床应用于糖尿病日益增多,有关它改善胰岛β细胞功能机制研究不断深入,尤其是有关内质网应激方面的研究,现对此综述如下。     

胰高血糖素样肽-1的分泌释放和降糖作用机制及临床应用进展

胰高血糖素样肽-1是近年来2型糖尿病治疗方面的研究热点之一。它是由小肠上皮L细胞分泌的一种肽类物质,对维持餐后血糖和控制食欲起到重要作用。本文从胰高血糖素样肽-1的分泌释放机制、降血糖作用机制和已开发药物的临床效果三方面进行综述。     

胰高血糖素样肽-1--2型糖尿病治疗的新策略

胰高血糖素样肽-1(GLP-1)由胰岛α细胞和肠道L细胞分泌,具有葡萄糖依赖性促胰岛素分泌、抑制胰高血糖素产生、增加β细胞数量及延缓胃排空等作用。易被二肽基肽酶IV(DPP-IV)降解,半衰期(t1/2)仅数分钟。近来,GLP-1类似物和DPP-IV抑制剂的研发为2型糖尿病的治疗提供了新策略。     

Incretin-based therapies for type 2 diabetes mellitus: a review of direct comparisons of efficacy, safety and patient satisfaction

Background Clinical trials comparing incretin-based therapies—glucagon-like peptide-1 receptor agonists (exenatide—twice daily and once weekly—and once-daily liraglutide) and dipeptidyl peptidase-4 inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin)—with placebo and oral antidiabetic drugs show that these therapies effectively control glycaemia, with low risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists are associated with weight loss and reductions in systolic blood pressure, while dipeptidyl peptidase-4 inhibitors are weight-neutral. Based on this, the National Institute for Health and Clinical Excellence recommends using these agents in patients with type 2 diabetes for whom excess weight and/or hypoglycaemia are problematic. Aim of the review This review aims to help decision making when selecting and using incretin-based therapies in type 2 diabetes. Methods A search or MEDLINE and Cochrane clinical trials databases, limited to clinical trials in humans, was performed using the search criteria ‘exenatide or liraglutide or vildagliptin or sitagliptin, or saxagliptin or linagliptin’. Abstracts presented at recent American Diabetes Association and European Association for the Study of Diabetes meetings were also searched. Eighteen clinical trials directly comparing incretin-based therapies were identified. Results Glucagon-like peptide-1 receptor agonists achieved significantly greater reductions in glycated hemoglobin and weight than dipeptidyl peptidase-4 inhibitors, which have a neutral effect on weight. Between-treatment differences were clinically important. Gastrointestinal side effects were more frequent with glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors. Comparisons between glucagon-like peptide-1 receptor agonists and between dipeptidyl peptidase-4 inhibitors showed that differences within the available agents in the two sub-classes are small. Greater treatment satisfaction was reported with glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors. Conclusion Glucagon-like peptide-1 receptor agonists achieve greater glycated hemoglobin reductions than dipeptidyl peptidase-4 inhibitors, with concomitant weight loss. Probably due to the greater efficacy of glucagon-like peptide-1 receptor agonists, patient satisfaction is greater with these agents compared with dipeptidyl peptidase-4 inhibitors despite injectable versus oral administration and more frequent gastrointestinal side effects with the agonists.     

苦味中药激活肠道苦味受体分泌胰高血糖素样肽-1的研究现状

胰高血糖素样肽-1(GLP-1)可以刺激胰岛素释放以及抑制胰高血糖素释放,与2型糖尿病有关。苦味中药可以激活肠道上的苦味受体(TAS2Rs),通过磷脂酶C通路和磷酸二酯酶通路刺激肠道内分泌L细胞未分泌GLP-1,广泛用于2型糖尿病的防治。本文综述了苦味中药对肠道TAS2Rs介导的GLP-1分泌的调控作用,为苦味中药防治2型糖尿病提供新视角。     

利拉鲁肽的临床应用及其作用机制的研究进展

胰高血糖素样肽-1(GLP-1)是小肠消化食物时L细胞分泌的一种促胰岛素激素,可以促进胰岛素分泌,从而维持葡萄糖稳态,其受体广泛分布于胰岛、心脏、肺、皮肤等器官中.利拉鲁肽是一种长效的GLP-1类似物,目前被广泛用于治疗2型糖尿病.近年来研究发现,利拉鲁肽在肥胖症、神经系统疾病、心血管系统疾病中均发挥有益作用.对利拉鲁肽治疗糖尿病、肥胖症、神经系统疾病、心血管系统疾病和精神疾病等的临床研究及其作用机制进行综述,旨在为拓展和开发利拉鲁肽类药物的临床应用提供新思路.     

Glucagon-like peptide-1, a gastrointestinal hormone with a pharmaceutical potential.

Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted from endocrine cells in the gut mucosa in response to meal ingestion. It is an important incretin hormone; mice with a null mutation in the GLP-1 receptor gene develop glucose intolerance. In addition, it inhibits gastrointestinal secretion and motility and is thought to be part of the "ileal brake" mechanism. Perhaps because of the latter actions it inhibits food intake, but intracerebral injection of GLP-1 also inhibits food intake. The insulinotropic effect is preserved in patients with type 2 diabetes mellitus, in whom also glucagon secretion is inhibited. Thus upon i.v. GLP-1 infusion blood glucose may be completely normalised. Because its actions are glucose-dependent hypoglycaemia does not develop. However, GLP-1 is metabolised extremely rapidly in vivo, initially by a mechanism that involves the enzyme dipeptidyl peptidase-IV. It is currently being investigated how GLP-1 or analogues thereof can be employed in practical diabetes therapy. Promising solutions include the development of stable analogues and inhibitors of the degrading enzyme.     

胰高血糖素样肽-1及相关降糖药物的研究进展

胰高血糖素样肽-1（glucagon-like peptide-1,GLP-1）是近几年糖尿病治疗药物研究的热点之一,具备多重降血糖作用。它的两大类药物：GLP-1类似物和二肽基肽酶-Ⅳ抑制剂作为新的降糖药物相继完成临床研究,并在糖尿病治疗中发挥越来越重要的作用。本文就GLP-1的结构、药理作用以及两类相关降糖药物的临床应用作一概述。     

人GLP-1类似物治疗2型糖尿病的研究进展

人胰高血糖素样肽1（GLP-1）类似物已成为新一代降糖药。无论是上市的艾塞那肽和利拉鲁肽,还是处于临床研究阶段的taspoglutide,均在2型糖尿病临床研究中取得显著成果,如有效降糖、减轻体重和减少低血糖发生等。同时,人GLP—1类似物潜在的益处与风险还有待进一步研究。