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作为评估二肽基肽酶4(DPP4)抑制剂降血糖作用的快速筛选模型:DPP4的高度进化保守性。

as a Rapid Screening Model to Evaluate the Hypoglycemic Effects of Dipeptidyl Peptidase 4 (DPP4) Inhibitors: High Evolutionary Conservation of DPP4.

作者信息

Lagunas-Rangel Francisco Alejandro, Liao Sifang, Williams Michael J, Trukhan Vladimir, Fredriksson Robert, Schiöth Helgi B

机构信息

Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.

Advanced Molecular Technology LLC, 354 340 Moscow, Russia.

出版信息

Biomedicines. 2023 Nov 12;11(11):3032. doi: 10.3390/biomedicines11113032.

Abstract

Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, have been an integral part of the treatment of type 2 diabetes mellitus (T2DM) for several years. Despite their remarkable efficacy in lowering glucose levels and their compatibility with other hypoglycemic drugs, recent studies have revealed adverse effects, prompting the search for improved drugs within this category, which has required the use of animal models to verify the hypoglycemic effects of these compounds. Currently, in many countries the use of mammals is being significantly restricted, as well as cost prohibitive, and alternative in vivo approaches have been encouraged. In this sense, has emerged as a promising alternative for several compelling reasons: it is cost-effective, offers high experimental throughput, is genetically manipulable, and allows the assessment of multigenerational effects, among other advantages. In this study, we present evidence that diprotin A, a DPP4 inhibitor, effectively reduces glucose levels in hemolymph. This discovery underscores the potential of as an initial screening tool for novel compounds directed against DPP4 enzymatic activity.

摘要

二肽基肽酶4(DPP4)抑制剂,通常称为格列汀类药物,多年来一直是2型糖尿病(T2DM)治疗的重要组成部分。尽管它们在降低血糖水平方面具有显著疗效,并且与其他降糖药物具有兼容性,但最近的研究揭示了其不良反应,促使人们在这一类药物中寻找改进药物,这需要使用动物模型来验证这些化合物的降糖作用。目前,在许多国家,哺乳动物的使用受到显著限制,而且成本高昂,因此鼓励采用替代的体内研究方法。从这个意义上说,由于几个令人信服的原因, 已成为一种有前途的替代方法:它具有成本效益、实验通量高、可进行基因操作,并允许评估多代效应等优点。在本研究中,我们提供证据表明,DPP4抑制剂双丙谷酰胺A可有效降低 血淋巴中的葡萄糖水平。这一发现强调了 作为针对DPP4酶活性的新型化合物的初步筛选工具的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2610/10669173/c9359b0bb629/biomedicines-11-03032-g001.jpg

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