Metformin Effect on Nontargeted Metabolite Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues.

Adam, Jonathan; Brandmaier, Stefan; Leonhardt, Jörn; Scheerer, Markus F; Mohney, Robert P; Xu, Tao; Bi, Jie; Rotter, Markus; Troll, Martina; Chi, Shen; Heier, Margit; Herder, Christian; Rathmann, Wolfgang; Giani, Guido; Adamski, Jerzy; Illig, Thomas; Strauch, Konstantin; Li, Yixue; Gieger, Christian; Peters, Annette; Suhre, Karsten; Ankerst, Donna; Meitinger, Thomas; Hrab? de Angelis, Martin; Roden, Michael; Neschen, Susanne; Kastenmüller, Gabi; Wang-Sattler, Rui

doi:10.2337/db16-0512

Benutzer: Gast

journal article

Titel:: Metformin Effect on Nontargeted Metabolite Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues.
Dokumenttyp:: Journal Article; Article
Autor(en):: Adam, Jonathan; Brandmaier, Stefan; Leonhardt, Jörn; Scheerer, Markus F; Mohney, Robert P; Xu, Tao; Bi, Jie; Rotter, Markus; Troll, Martina; Chi, Shen; Heier, Margit; Herder, Christian; Rathmann, Wolfgang; Giani, Guido; Adamski, Jerzy; Illig, Thomas; Strauch, Konstantin; Li, Yixue; Gieger, Christian; Peters, Annette; Suhre, Karsten; Ankerst, Donna; Meitinger, Thomas; Hrab? de Angelis, Martin; Roden, Michael; Neschen, Susanne; Kastenmüller, Gabi; Wang-Sattler, Rui
Abstract:: Metformin is the first-line oral medication to increase insulin sensitivity in patients with type 2 diabetes (T2D). Our aim was to investigate the pleiotropic effect of metformin using a nontargeted metabolomics approach. We analyzed 353 metabolites in fasting serum samples of the population-based human KORA (Cooperative Health Research in the Region of Augsburg) follow-up survey 4 cohort. To compare T2D patients treated with metformin (mt-T2D, n = 74) and those without antidiabetes medication (ndt-T2D, n = 115), we used multivariable linear regression models in a cross-sectional study. We applied a generalized estimating equation to confirm the initial findings in longitudinal samples of 683 KORA participants. In a translational approach, we used murine plasma, liver, skeletal muscle, and epididymal adipose tissue samples from metformin-treated db/db mice to further corroborate our findings from the human study. We identified two metabolites significantly (P < 1.42E-04) associated with metformin treatment. Citrulline showed lower relative concentrations and an unknown metabolite X-21365 showed higher relative concentrations in human serum when comparing mt-T2D with ndt-T2D. Citrulline was confirmed to be significantly (P < 2.96E-04) decreased at 7-year follow-up in patients who started metformin treatment. In mice, we validated significantly (P < 4.52E-07) lower citrulline values in plasma, skeletal muscle, and adipose tissue of metformin-treated animals but not in their liver. The lowered values of citrulline we observed by using a nontargeted approach most likely resulted from the pleiotropic effect of metformin on the interlocked urea and nitric oxide cycle. The translational data derived from multiple murine tissues corroborated and complemented the findings from the human cohort.
Zeitschriftentitel:: Diabetes
Jahr:: 2016
Band / Volume:: 65
Heft / Issue:: 12
Seitenangaben Beitrag:: 3776-3785
Sprache:: eng
Volltext / DOI:: doi:10.2337/db16-0512
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/27621107
Print-ISSN:: 0012-1797
TUM Einrichtung:: Institut für Humangenetik
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Institut für Humangenetik (Prof. Winkelmann)2016