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Emerging Therapeutic Targets in Regenerative Medicine for the Treatment of Diabetes Mellitus: A Patent Literature Review

机译:再生医学中治疗糖尿病的新兴治疗目标:专利文献综述

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In recent years, the concept of preserving and/or replenishing the functional beta-cell mass vital to sustain insulin output and normalized blood glucose levels has gained much interest as a therapeutic approach in regenerative medicine for the treatment of Diabetes Mellitus. Herein, we surveyed the diabetes area patent literature published in recent years to identify novel uprising therapeutic targets specifically implicated in regeneration and survival. One hundred and sixty nine international patent applications filed under the Patent Cooperation Treaty (PCT) (hereinafter, patents or applications) were highlighted from which 8 particular targets stood out with more than 4 patents published within the last few years. Not surprisingly, GLP-1 analogues and DPP-4 inhibitors along with GPR119 agonists and SGLT2 inhibitors were among the top ranked candidates. However, new emerging targets into the field of regenerative medicine for the treatment of diabetes include: 1) BACE-2; a protease that was recently shown to cleave the plasma membrane glycoprotein TMEM27 (also called collectrin) resulting in the inhibition of pancreatic beta cell proliferation and insulin secretion, 2) GIP; a 42 amino acid incretin hormone that potentiates glucose induce insulin secretion and protect p-cells against cytokine-mediated apoptosis, 3) neurturin; a neurotrophic factor capable of improving blood glucose levels in high fat diet treated animals, and 4) LRH-1, an orphan nuclear receptor that improves islet viability. These novel targets along with GPR119 are further discussed in this review.
机译:近年来,保存和/或补充对于维持胰岛素输出和血糖水平正常化至关重要的功能性β-细胞团的概念作为治疗糖尿病的再生医学的治疗方法引起了广泛兴趣。在这里,我们调查了近年来发表的糖尿病领域专利文献,以鉴定特别与再生和存活有关的新型起义治疗靶标。重点介绍了根据专利合作条约(PCT)提交的169项国际专利申请(以下称专利或申请),其中有8个具体目标突出,在最近几年中公开了4多项专利。毫不奇怪,GLP-1类似物和DPP-4抑制剂以及GPR119激动剂和SGLT2抑制剂是排名最高的候选药物。然而,用于治疗糖尿病的再生医学领域的新兴目标包括:1)BACE-2;最近被证明可裂解质膜糖蛋白TMEM27(也称为collectrin)的蛋白酶,可抑制胰腺β细胞增殖和胰岛素分泌,2)GIP;增强葡萄糖的42个氨基酸的肠降血糖素激素可诱导胰岛素分泌并保护p细胞免于细胞因子介导的细胞凋亡; 3)神经营养素;一种能够改善经高脂饮食治疗的动物的血糖水平的神经营养因子,以及4)LRH-1(一种提高胰岛生存能力的孤儿核受体)。这些新颖的目标与GPR119一起在本综述中进一步讨论。

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