Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry.
10.12793/tcp.2017.25.2.67
- Author:
Eun Young DO
1
;
Mi Ri GWON
;
Bo Kyung KIM
;
Boram OHK
;
Hae Won LEE
;
Woo Youl KANG
;
Sook Jin SEONG
;
Hyun Ju KIM
;
Young Ran YOON
Author Information
1. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Cell and Matrix Research Institute, and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu 41944, Korea. yry@knu.ac.kr, biohjk@knu.ac.kr
- Publication Type:Original Article
- Keywords:
metabolomic profiling;
glimepiride;
liquid chromatographytandem mass spectrometry
- MeSH:
Adenosine;
Diabetes Mellitus, Type 2;
Histidine;
Humans*;
Insulin;
Least-Squares Analysis;
Male;
Mass Spectrometry*;
Metabolism;
Metabolomics*;
Principal Component Analysis;
Quercetin;
Statistics as Topic;
Tyramine;
Tyrosine;
Urocanic Acid;
Volunteers
- From:Translational and Clinical Pharmacology
2017;25(2):67-73
- CountryRepublic of Korea
- Language:English
-
Abstract:
Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3′, 5′-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.
