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小肠蛋白质组学与血清代谢组学相结合揭示了 2 型糖尿病中国仓鼠氨基酸代谢的紊乱。

Small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in Chinese hamsters with type 2 diabetes mellitus.

机构信息

Labratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan 030001, China.

School of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China.

出版信息

J Proteomics. 2020 Jul 15;223:103823. doi: 10.1016/j.jprot.2020.103823. Epub 2020 May 16.

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (IR), or both. Chinese hamsters have potential value as non-obese animal models of spontaneous T2DM for studying the pathogenesis and molecular characteristics of diabetes. In this study, the molecular characteristics of the Chinese hamster diabetes animal model were investigated through small intestine proteomics and serum metabolomics. A total of 213 differentially abundant proteins and 14 differentially abundant metabolites were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight mass spectrometry (GC-TOF/MS) analysis, respectively. Annotation by bioinformatics analysis revealed that these differentially abundant proteins in the small intestine were commonly associated with abnormal glucose and lipid metabolism, IR, impaired insulin secretion, amino acid metabolism disorders, and inflammatory dysregulation. Moreover, differentially abundant metabolites in the serum were amino acids and were related to diabetic IR. Through the analysis of small intestine proteomics and serum metabolomics in the Chinese hamster diabetes model, we provide a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. This study provides data incentivizing the popularization and application of Chinese hamsters in T2DM research. SIGNIFICANCE: Spontaneous rodent models of diabetes, such as Chinese hamsters, effectively summarizes the clinical characteristics of type 2 diabetes and has high applicative value for studying the pathophysiology of diabetes. In order to explore the potential value of the Chinese hamster diabetes animal model in the study of the T2DM molecular mechanism, we performed small intestine proteomic analysis and serum metabolomic analysis in Chinese hamsters for the first time. After an integrated analysis of proteomics and metabolomics, we have a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. Further, we found that in the occurrence and development of T2DM, the metabolic abnormalities of this model are particularly prominent, especially the metabolism of amino acids. These findings not only provide basic data in support of the popularization and application of the current model in T2DM research, but also provide a new perspective for the exploration of mechanisms related to T2DM.

摘要

2 型糖尿病(T2DM)是一种以高血糖为特征的代谢紊乱,其代谢紊乱是由于胰岛素分泌缺陷、胰岛素抵抗(IR)或两者兼而有之。中国仓鼠具有作为自发性 2 型糖尿病非肥胖动物模型的潜力,可用于研究糖尿病的发病机制和分子特征。本研究通过小肠蛋白质组学和血清代谢组学研究了中国仓鼠糖尿病动物模型的分子特征。通过液相色谱-串联质谱(LC-MS/MS)和气相色谱-飞行时间质谱(GC-TOF/MS)分析分别鉴定出 213 个差异丰度蛋白和 14 个差异丰度代谢物。通过生物信息学分析注释发现,这些小肠中差异丰度蛋白与葡萄糖和脂质代谢异常、IR、胰岛素分泌受损、氨基酸代谢紊乱和炎症失调有关。此外,血清中差异丰度代谢物为氨基酸,与糖尿病 IR 有关。通过对中国仓鼠糖尿病模型的小肠蛋白质组学和血清代谢组学分析,从分子角度初步了解了该模型的糖尿病特征。本研究为中国仓鼠在 T2DM 研究中的推广应用提供了数据支持。意义:自发性糖尿病啮齿动物模型,如中国仓鼠,有效总结了 2 型糖尿病的临床特征,对于研究糖尿病的病理生理学具有很高的应用价值。为了探讨中国仓鼠糖尿病动物模型在 2 型糖尿病分子机制研究中的潜在价值,我们首次对中国仓鼠进行了小肠蛋白质组学分析和血清代谢组学分析。通过蛋白质组学和代谢组学的综合分析,我们从分子角度初步了解了该模型的糖尿病特征。此外,我们发现,在 2 型糖尿病的发生和发展过程中,该模型的代谢异常尤为突出,特别是氨基酸代谢。这些发现不仅为当前模型在 2 型糖尿病研究中的推广应用提供了基础数据支持,也为探索与 2 型糖尿病相关的机制提供了新的视角。

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