title: Urinary metabolomic profiling in mice with diet-induced obesity and type 2 diabetes mellitus after treatment with metformin, vildagliptin and their combination.
abstract: Metformin, vildagliptin and their combination are widely used for the treatment of diabetes, but little is known about the metabolic responses to these treatments. In the present study, NMR-based metabolomics was applied to detect changes in the urinary metabolomic profile of a mouse model of diet-induced obesity in response to these treatments. Additionally, standard biochemical parameters and the expression of enzymes involved in glucose and fat metabolism were monitored. Significant correlations were observed between several metabolites (e.g., N-carbamoyl-β-alanine, N1-methyl-4-pyridone-3-carboxamide, N1-methyl-2-pyridone-5-carboxamide, glucose, 3-indoxyl sulfate, dimethylglycine and several acylglycines) and the area under the curve of glucose concentrations during the oral glucose tolerance test. The present study is the first to present N-carbamoyl-β-alanine as a potential marker of type 2 diabetes mellitus and consequently to demonstrate the efficacies of the applied antidiabetic interventions. Moreover, the elevated acetate level observed after vildagliptin administration might reflect increased fatty acid oxidation.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Czech Republic; Department of Analytical Chemistry, Faculty of Science, Palacký University, 17 listopadu 1192/12, 771 46, Olomouc, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Pelantová
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Czech Republic; Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Bugáňová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Holubová
authors.affiliation: Faculty of Applied Sciences, University of West Bohemia, Univerzitní 8, 306 14, Plzeň, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Šedivá
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic; Faculty of Chemical Engineering, University of Chemistry and Technology Prague, Technická 3, 166 28, Prague 6, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Zemenová
authors.affiliation: Faculty of Chemical Engineering, University of Chemistry and Technology Prague, Technická 3, 166 28, Prague 6, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Sýkora
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General Faculty Hospital in Prague, U nemocnice 1, 128 08, Prague 2, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Kaválková
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General Faculty Hospital in Prague, U nemocnice 1, 128 08, Prague 2, Czech Republic; Institute of Endocrinology, Národní 8, 116 94, Prague 1, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Haluzík
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Železná
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic; Institute of Physiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kuneš
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Czech Republic. Electronic address: kuzma@biomed.cas.cz.
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D004032:Diet; D005951:Glucose Tolerance Test / Q000379:methods; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D055432:Metabolomics / Q000379:methods; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D011728:Pyridones / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D000077597:Vildagliptin; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D009570:Nitriles; D011728:Pyridones; D011759:Pyrrolidines; D015091:beta-Alanine; C534143:4-pyridone; C035122:N-carbamoyl-beta-alanine; C017679:2-hydroxypyridine; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane
keywords: Antidiabetic treatment; Mouse; NMR metabolomics; Obesity; Type 2 diabetes mellitus; Urine