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研究药物在体内和体外抗糖尿病活性的实验模型进展。

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs.

机构信息

School of Pharmacy & Health Sciences, United States International University-AFRICA (USIU-A), Nairobi, Kenya.

Department of Pharmaceutical Chemistry, Geethanjali College of Pharmacy, Keesara, India.

出版信息

Animal Model Exp Med. 2024 Jun;7(3):297-309. doi: 10.1002/ame2.12442. Epub 2024 Jun 4.

Abstract

Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by hyperglycemia, a condition involving a high blood glucose level brought on by deficiencies in insulin secretion, decreased activity of insulin, or both. Prolonged effects of diabetes include cardiovascular problems, retinopathy, neuropathy, nephropathy, and vascular alterations in both macro- and micro-blood vessels. In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis, identifying targets, and reviewing novel treatment options and medications. Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences. The most popular in vivo studies involves the small animal models, such as rodent models, chemically induced diabetogens like streptozotocin and alloxan, and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals. Other models include virally induced models, diet/nutrition induced diabetic animals, surgically induced models or pancreatectomy models, and non-obese models. Large animals or non-rodent models like porcine (pig), canine (dog), nonhuman primate, and Zebrafish models are also outlined. The in vitro models discussed are murine and human beta-cell lines and pancreatic islets, human stem cells, and organoid cultures. The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition of α-glucosidase activity.

摘要

糖尿病是世界上最普遍和复杂的代谢紊乱之一,也是一个迅速增长的全球公共卫生问题。它的特征是高血糖,这是一种由于胰岛素分泌不足、胰岛素活性降低或两者兼而有之导致的高血糖状态。糖尿病的长期影响包括心血管问题、视网膜病变、神经病变、肾病和大、微血管的血管改变。体内和体外模型一直是研究和描述疾病发病机制、确定靶点以及审查新的治疗选择和药物的重要手段。充分了解这些模型对研究人员来说至关重要,因此本综述总结了用于研究糖尿病及其后果的不同体内和体外实验模型选择。最受欢迎的体内研究涉及小型动物模型,如啮齿动物模型、化学诱导的糖尿病原代细胞,如链脲佐菌素和别嘌呤醇,以及通过敲除和转基因技术在这些动物上删除或过表达特定基因的可能性。其他模型包括病毒诱导模型、饮食/营养诱导的糖尿病动物、手术诱导模型或胰腺切除术模型,以及非肥胖模型。大型动物或非啮齿动物模型,如猪(猪)、犬(狗)、非人类灵长类动物和斑马鱼模型也有介绍。讨论的体外模型包括鼠和人β细胞系和胰岛、人干细胞和类器官培养物。评估糖尿病的其他酶学体外试验包括淀粉酶抑制测定和α-葡萄糖苷酶活性抑制测定。

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