Metabonomic study of biochemical changes in the serum of type 2 diabetes mellitus patients after the treatment of metformin hydrochloride

被引:114
作者
Huo, Taoguang [1 ]
Cai, Shuang [1 ,2 ]
Lu, Xiumei [1 ]
Sha, Yi [1 ]
Yu, Mingyang [1 ]
Li, Famei [1 ]
机构
[1] Shenyang Pharmaceut Univ, Dept Analyt Chem, Shenyang 110016, Peoples R China
[2] China Med Univ, Affiliated Hosp 1, Shenyang 110001, Peoples R China
关键词
H-1; NMR; UPLC/MS; Type 2 diabetes mellitus; Metabolite profiles; Metformin hydrochloride; MAGNETIC-RESONANCE-SPECTROSCOPY; TOF MASS-SPECTROMETRY; RAT URINE; HPLC-MS; H-1-NMR SPECTROSCOPY; NMR; ZUCKER; PLASMA; METHYLAMINES; METHODOLOGY;
D O I
10.1016/j.jpba.2009.01.008
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A metabonomic study on biochemical changes in the serum of type 2 diabetes mellitus patients after the treatment of metformin hydrochloride was performed. H-1 NMR and UPLC/MS were used to generate metabolic fingerprints for the metabonomic analysis of serum samples obtained from 20 type 2 diabetes mellitus patients without any drugs treatment and 15 type 2 diabetes mellitus patients treated with metformin hydrochloride for 3 months. The resulting data were subjected to chemometric analysis (principal component analysis and partial least squares discriminant analysis) to investigate the effect of metformin hydrochloride on serum metabolite profiles of type 2 diabetes mellitus patients. I H NMR spectroscopic analysis revealed increased trimethylamine-N-oxide (TMAO), 3-hydroxybutyrate (3-HB) and decreased glucose, N-acetyl glycoprotein (NAC), lipoprotein, lactate, acetoacetate and unsaturated lipids in serum from metformin treated patients compared to untreated ones. UPLC/MS in positive electrospray ionization detected increased tryptophan and decreased lysophosphatidylcholines (C16:0 LPC, C18:0 LPC and C18:2 LPC) as well as phenylalanine in treated group. Both analytical techniques used in this study were able to detect biochemical changes in the serum of type 2 diabetes mellitus patients after the treatment of metformin hydrochloride, which may be helpful to the understanding of action mechanism of metformin hydrochloride. (c) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:976 / 982
页数:7
相关论文
共 47 条
[21]   Lipid-induced β-cell dysfunction and oxidative stress [J].
Oprescu, Andrei I. ;
Giacca, Adria .
FUTURE LIPIDOLOGY, 2007, 2 (04) :455-463
[22]   Metabonomic analysis of mouse urine by liquid-chromatography-time of flight mass spectrometry (LC-TOFMS): detection of strain, diurnal and gender differences [J].
Plumb, R ;
Granger, J ;
Stumpf, C ;
Wilson, ID ;
Evans, JA ;
Lenz, EM .
ANALYST, 2003, 128 (07) :819-823
[23]   UPLC/MSE;: a new approach for generating molecular fragment information for biomarker structure elucidation [J].
Plumb, Robert S. ;
Johnson, Kelly A. ;
Rainville, Paul ;
Smith, Brian W. ;
Wilson, Ian D. ;
Castro-Perez, Jose M. ;
Nicholson, Jeremy K. .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2006, 20 (13) :1989-1994
[24]   A rapid screening approach to metabonomics using UPLC and oa-TOF mass spectrometry: application to age, gender and diurnal variation in normal/Zucker obese rats and black, white and nude mice [J].
Plumb, RS ;
Granger, JH ;
Stumpf, CL ;
Johnson, KA ;
Smith, BW ;
Gaulitz, S ;
Wilson, ID ;
Castro-Perez, J .
ANALYST, 2005, 130 (06) :844-849
[25]   Metabonomics: the use of electrospray mass spectrometry coupled to reversed-phase liquid chromatography shows potential for the screening of rat urine in drug development [J].
Plumb, RS ;
Stumpf, CL ;
Gorenstein, MV ;
Castro-Perez, JM ;
Dear, GJ ;
Anthony, M ;
Sweatman, BC ;
Connor, SC ;
Haselden, JN .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2002, 16 (20) :1991-1996
[26]   Multivariate classification analysis of metabolomic data for candidate biomarker discovery in type 2 diabetes mellitus [J].
Qiu, Yang ;
Rajagopalan, Dilip ;
Connor, Susan C. ;
Damian, Doris ;
Zhu, Lei ;
Handzel, Amir ;
Hu, Guanghui ;
Amanullah, Arshad ;
Bao, Steve ;
Woody, Nathaniel ;
MacLean, David ;
Lee, Kwan ;
Vanderwall, Dana ;
Ryan, Terence .
METABOLOMICS, 2008, 4 (04) :337-346
[27]   METABOLISM AND EXCRETION OF METHYLAMINES IN RATS [J].
SMITH, JL ;
WISHNOK, JS ;
DEEN, WM .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1994, 125 (02) :296-308
[28]   Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS [J].
Sun, Jinchun ;
Schnackenberg, Laura K. ;
Holland, Ricky D. ;
Schmitt, Thomas C. ;
Cantor, Glenn H. ;
Dragan, Yvonne R. ;
Beger, Richard D. .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2008, 871 (02) :328-340
[29]   Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small metabolites in blood plasma [J].
Tang, HR ;
Wang, YL ;
Nicholson, JK ;
Lindon, JC .
ANALYTICAL BIOCHEMISTRY, 2004, 325 (02) :260-272
[30]   LC-MS-based methodology for global metabolite profiling in metabonomics/metabolomics [J].
Theodoridis, Georgios ;
Gika, Helen G. ;
Wilson, Ian D. .
TRAC-TRENDS IN ANALYTICAL CHEMISTRY, 2008, 27 (03) :251-260