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糖尿病尿外泌体中与有氧氧化代谢相关蛋白的差异表达。

Differential expression of aerobic oxidative metabolism-related proteins in diabetic urinary exosomes.

机构信息

Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.

出版信息

Front Endocrinol (Lausanne). 2022 Sep 14;13:992827. doi: 10.3389/fendo.2022.992827. eCollection 2022.

Abstract

BACKGROUND

As a metabolic disease, any abnormality in the aerobic oxidation pathway of glucose may lead to the occurrence of diabetes. This study aimed to investigate the changes in proteins related to aerobic oxidative metabolism in urinary exosomes of diabetic patients and normal controls of different ages, and to further verify their correlation with the pathogenesis of diabetes.

METHODS

Samples were collected, and proteomic information of urinary exosomes was collected by LC-MS/MS. ELISA was used to further detect the expression of aerobic and oxidative metabolism-related proteins in urinary exosomes of diabetic patients and normal controls of different ages, and to draw receiver operating characteristic (ROC) curve to evaluate its value in diabetes monitoring.

RESULTS

A total of 17 proteins involved in aerobic oxidative metabolism of glucose were identified in urinary exosome proteins. Compared with normal control, the expressions of PFKM, GAPDH, ACO2 and MDH2 in diabetic patients were decreased, and the expression of IDH3G was increased. The concentrations of PFKM, GAPDH and ACO2 in urinary exosomes were linearly correlated with the expression of MDH2 (P<0.05). These four proteins vary with age, with the maximum concentration in the 45-59 age group. PFKM, GAPDH, ACO2, and MDH2 in urinary exosomes have certain monitoring value. When used in combination, the AUC was 0.840 (95% CI 0.764-0.915).

CONCLUSIONS

In diabetic patients, aerobic oxidative metabolism is reduced, and the expression of aerobic oxidative metabolism-related proteins PFKM, GAPDH, ACO2, and MDH2 in urinary exosomes is reduced, which may become potential biomarkers for monitoring changes in diabetes.

摘要

背景

作为一种代谢疾病,葡萄糖有氧氧化途径的任何异常都可能导致糖尿病的发生。本研究旨在探讨不同年龄段糖尿病患者和正常对照者尿外泌体中与有氧氧化代谢相关的蛋白质的变化,并进一步验证其与糖尿病发病机制的相关性。

方法

采集样本,通过 LC-MS/MS 收集尿外泌体的蛋白质组学信息,采用 ELISA 法进一步检测不同年龄段糖尿病患者和正常对照者尿外泌体中与有氧氧化代谢相关的蛋白质的表达情况,并绘制受试者工作特征(ROC)曲线评估其在糖尿病监测中的价值。

结果

共鉴定出 17 种参与葡萄糖有氧氧化代谢的尿外泌体蛋白。与正常对照组相比,糖尿病患者尿外泌体中 PFKM、GAPDH、ACO2 和 MDH2 的表达降低,IDH3G 的表达升高。尿外泌体中 PFKM、GAPDH 和 ACO2 的浓度与 MDH2 的表达呈线性相关(P<0.05)。这四种蛋白质随年龄变化,在 45-59 岁年龄组中浓度最高。尿外泌体中的 PFKM、GAPDH、ACO2 和 MDH2 具有一定的监测价值,联合使用时 AUC 为 0.840(95%CI 0.764-0.915)。

结论

在糖尿病患者中,有氧氧化代谢减少,尿外泌体中与有氧氧化代谢相关的蛋白质 PFKM、GAPDH、ACO2 和 MDH2 的表达减少,可能成为监测糖尿病变化的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8b4/9515495/6d4883488ac1/fendo-13-992827-g001.jpg

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