Metformin Scavenges Methylglyoxal To Form a Novel Imidazolinone Metabolite in Humans

Chemical Research in Toxicology
Owen R KinskySerrine S Lau

Abstract

Methylglyoxal (MG) is a highly reactive dicarbonyl compound involved in the formation of advanced glycation endproducts (AGE). Levels of MG are elevated in patients with type-2 diabetes mellitus (T2DM), and AGE have been implicated in the progression of diabetic complications. The antihyperglycemic drug metformin (MF) has been suggested to be a scavenger of MG. The present work examined and characterized unequivocally the resulting scavenged product from the metformin-MG reaction. The primary product was characterized by (1)H, (13)C, 2D-HSQC, and HMBC NMR and tandem mass spectrometry. X-ray diffraction analysis determined the structure of the metformin and MG-derived imidazolinone compound as (E)-1,1-dimethyl-2-(5-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)guanidine (IMZ). A LC-MS/MS multiple reaction monitoring method was developed to detect and quantify the presence of IMZ in metformin-treated T2DM patients. Urine from >90 MF-treated T2DM patients was analyzed, with increased levels of MF directly correlating with elevations in IMZ. Urinary MF was detected in the range of 0.17 μM to 23.0 mM, and simultaneous measurement of IMZ concentrations were in the range of 18.8 nM to 4.3 μM. Since plasma concentrations of MG range from 4...Continue Reading

References

Dec 1, 1978·Clinical Pharmacology and Therapeutics·C R SirtoriF Conti
Sep 23, 2003·Diabetes & Metabolism·P Beisswenger, D Ruggiero-Lopez
Nov 26, 2003·Investigative Ophthalmology & Visual Science·Naila AhmedGeorge M Haik
Jun 11, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Tadashi KihoKazuyuki Hirano
Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
Sep 2, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·M Y KhuhawarA J Laghari
Mar 21, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Arti DharLingyun Wu
Feb 22, 2011·Seminars in Cell & Developmental Biology·Naila Rabbani, Paul J Thornalley
Sep 3, 2011·Cardiovascular Therapeutics·Lincoln P EdwardsPaul Ernsberger
Feb 24, 2012·Pharmacological Reports : PR·Jerusalem TesfaiLincoln P Edwards
Apr 12, 2012·Cardiorenal Medicine·Hussein YassineSerrine S Lau
Dec 5, 2012·Diabetes Research and Clinical Practice·Miklós Péter Kalapos
Mar 14, 2014·Diabetes Care·Christian HamppDiane K Wysowski
Mar 22, 2014·Biochemical Society Transactions·Naila Rabbani, Paul J Thornalley
Mar 22, 2014·Biochemical Society Transactions·Paul J Beisswenger
Mar 22, 2014·Biochemical Society Transactions·Paul J Thornalley, Naila Rabbani
Apr 9, 2014·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Z KenderP P Nawroth

❮ Previous
Next ❯

Citations

Jul 19, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yuki OgasawaraMakoto Arai
Jul 14, 2016·Glycoconjugate Journal·Naila RabbaniPaul J Thornalley
Aug 27, 2016·The Journal of Physical Chemistry. a·Jan LangmaierStanislav Záliš
Sep 17, 2016·Medicinal Research Reviews·Paulo MatafomeRaquel Seiça
May 6, 2017·International Journal of Molecular Sciences·Sebastian BringsPeter P Nawroth
Nov 22, 2017·Antioxidants & Redox Signaling·Naila Rabbani, Paul J Thornalley
Nov 14, 2018·VASA. Zeitschrift für Gefässkrankheiten·Andreas S PetersMaani Hakimi
Feb 27, 2018·Journal of Parkinson's Disease·Annekatrin KönigTiago Fleming Outeiro
Dec 23, 2017·Frontiers in Neuroscience·Ryan B GriggsBradley K Taylor
May 18, 2019·Journal of Endocrinological Investigation·S E MeshkaniH Hosseinzadeh
Mar 27, 2020·International Journal of Molecular Sciences·Devang M PatelMark E Cooper
Sep 29, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Ingrid Delbone FigueiredoAmanda Martins Baviera
Dec 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katarzyna BednarskaIzabela Fecka
Jan 21, 2021·International Journal of Molecular Sciences·Faye K TsogasPeter C Hart
Sep 12, 2020·Current Research in Food Science·Raheleh Ghassem Zadeh, Varoujan Yaylayan
Feb 20, 2021·Frontiers in Oncology·Elisabet CuyàsJavier A Menendez
Jul 28, 2020·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Reham AliSayed M Saleh
Apr 20, 2021·Frontiers in Oncology·Alessia LeoneClaudia Miele
Jun 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Huong NguyenTerrence J Monks
Sep 5, 2017·Journal of Agricultural and Food Chemistry·Qiju HuangShengmin Sang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.