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靶向胰岛素受体的骆驼奶——深入了解骆驼奶的抗糖尿病作用

Camel Milk Targeting Insulin Receptor-Toward Understanding the Antidiabetic Effects of Camel Milk.

作者信息

Anwar Irfa, Khan Farheen Badrealam, Maqsood Sajid, Ayoub Mohammed Akli

机构信息

Department of Biology, College of Science, The United Arab Emirates University, Al Ain, United Arab Emirates.

Department of Food Science, College of Agriculture and Veterinary Medicine, The United Arab Emirates University, Al Ain, United Arab Emirates.

出版信息

Front Nutr. 2022 Feb 9;8:819278. doi: 10.3389/fnut.2021.819278. eCollection 2021.

Abstract

Camel milk (CM) is known for its beneficial virtues in the human diet and health. This includes its antidiabetic properties demonstrated in many and studies. Nevertheless, the scientific rationale behind the molecular and cellular basis of such beneficial effects and the exact antidiabetic agent(s)/mechanism(s) are still elusive. In this review, we focused on the recent advances supporting the targeting of insulin receptor (IR) by CM components. Indeed, our recent work reported that CM proteins and derived peptides pharmacologically target IR leading to its activation and potentiation of insulin-mediated responses. The review describes the experimental approaches used to investigate the effects of CM on IR based on the fractionation of CM whey proteins to purify functional proteins and their hydrolysis by gastric proteases to generate bioactive peptides. In addition, we illustrated our cellular and molecular model consisting of studying the functional activity of CM fractions on IR and its downstream signaling pathways in the hepatocarcinoma (HepG2) and the human embryonic kidney (HEK293) cells using the bioluminescence resonance energy transfer (BRET), phosphorylation, and glucose uptake assays. Overall, our work demonstrated for the first time that CM lactoferrin and CM-derived bioactive peptides positively modulate IR and its related signaling pathways in HepG2 and HEK293 cells. As a conclusion, the pharmacological targeting of IR by CM sheds more light on the antidiabetic properties of CM by providing its molecular basis that may constitute a solid rationale for the development of new generation of antidiabetic tools from CM-derived proteins and peptides and the utilization of CM in the management of diabetes. The sequencing and the synthesis of the potent bioactive CM peptides may open promising perspectives for their application as antidiabetic agents.

摘要

骆驼奶(CM)因其对人类饮食和健康的有益功效而闻名。这包括其在许多研究中所展现出的抗糖尿病特性。然而,这种有益作用在分子和细胞层面的科学原理以及确切的抗糖尿病因子/机制仍不明确。在本综述中,我们聚焦于支持骆驼奶成分靶向胰岛素受体(IR)的最新进展。事实上,我们最近的研究报告称,骆驼奶蛋白质及其衍生肽在药理学上靶向IR,从而导致其激活并增强胰岛素介导的反应。本综述描述了用于研究骆驼奶对IR影响的实验方法,这些方法基于对骆驼奶乳清蛋白进行分级分离以纯化功能蛋白,并通过胃蛋白酶对其进行水解以生成生物活性肽。此外,我们阐述了我们的细胞和分子模型,该模型包括利用生物发光共振能量转移(BRET)、磷酸化和葡萄糖摄取测定法,研究骆驼奶组分对肝癌(HepG2)细胞和人胚肾(HEK293)细胞中IR及其下游信号通路的功能活性。总体而言,我们的研究首次证明,骆驼奶乳铁蛋白和骆驼奶衍生的生物活性肽可正向调节HepG2和HEK293细胞中的IR及其相关信号通路。总之,骆驼奶对IR的药理学靶向作用通过提供其分子基础,为骆驼奶的抗糖尿病特性提供了更多见解,这可能为从骆驼奶衍生的蛋白质和肽开发新一代抗糖尿病工具以及在糖尿病管理中利用骆驼奶提供坚实的理论依据。强效生物活性骆驼奶肽的测序和合成可能为其作为抗糖尿病药物的应用开辟广阔前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee65/8864127/b3b0b4433297/fnut-08-819278-g0001.jpg

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