A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin

Background. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patien...

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Main Authors: Xiaoyu Liao, Bingyao Liu, Hua Qu, LinLin Zhang, Yongling Lu, Yong Xu, Zhaohui Lyu, Hongting Zheng
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/8247019
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author Xiaoyu Liao
Bingyao Liu
Hua Qu
LinLin Zhang
Yongling Lu
Yong Xu
Zhaohui Lyu
Hongting Zheng
author_facet Xiaoyu Liao
Bingyao Liu
Hua Qu
LinLin Zhang
Yongling Lu
Yong Xu
Zhaohui Lyu
Hongting Zheng
author_sort Xiaoyu Liao
collection DOAJ
description Background. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods. Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n=19), newly diagnosed T2D (n=20), placebo-treated T2D (n=7), or Sit-treated T2D (n=7). Biochemical parameters were also assessed in all participants. Results. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p<0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p<0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p<0.05). Conclusions. Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.
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spelling doaj-art-b0247a093f2a479b8321dff63d3d58722025-08-20T03:39:15ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/82470198247019A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of SitagliptinXiaoyu Liao0Bingyao Liu1Hua Qu2LinLin Zhang3Yongling Lu4Yong Xu5Zhaohui Lyu6Hongting Zheng7Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University (Former Name: Third Military Medical University), Chongqing, ChinaDepartment of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University (Former Name: Third Military Medical University), Chongqing, ChinaDepartment of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University (Former Name: Third Military Medical University), Chongqing, ChinaDepartment of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University (Former Name: Third Military Medical University), Chongqing, ChinaMedical Research Center, Southwest Hospital, Army Medical University (Former Name: Third Military Medical University), Chongqing, ChinaDepartment of Diabetes and Endocrinology, Affiliated Hospital of Southwest Medical University, Sichuan, ChinaThe Department and Key Laboratory of Endocrinology and Metabolism, The First Medical Center of PLA General Hospital, Beijing 100853, ChinaDepartment of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University (Former Name: Third Military Medical University), Chongqing, ChinaBackground. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods. Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n=19), newly diagnosed T2D (n=20), placebo-treated T2D (n=7), or Sit-treated T2D (n=7). Biochemical parameters were also assessed in all participants. Results. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p<0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p<0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p<0.05). Conclusions. Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.http://dx.doi.org/10.1155/2019/8247019
spellingShingle Xiaoyu Liao
Bingyao Liu
Hua Qu
LinLin Zhang
Yongling Lu
Yong Xu
Zhaohui Lyu
Hongting Zheng
A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin
Mediators of Inflammation
title A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin
title_full A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin
title_fullStr A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin
title_full_unstemmed A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin
title_short A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin
title_sort high level of circulating valine is a biomarker for type 2 diabetes and associated with the hypoglycemic effect of sitagliptin
url http://dx.doi.org/10.1155/2019/8247019
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