Pharmacometabolomic assessment of metformin in non-diabetic, African Americans

Frontiers in Pharmacology

Volumn 7, Issue JUN, 2016, Pages

  Rotroff, Daniel M ^a   Oki, Noffisat O ^a   Liang, Xiaomin ^b   Yee, Sook Wah ^b   Stocker, Sophie L ^b   Corum, Daniel G ^c   Meisner, Michele ^a   Fiehn, Oliver ^d,e   Motsinger Reif, Alison A ^a,f   Giacomini, Kathleen M ^b   Kaddurah Daouk, Rima ^f  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

^f DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Metabolism; Metformin; Pharmacometabolomics; Precision medicine

Indexed keywords

2 HYDROXYBUTANOIC ACID; GLUCOSE; HYDROXYACID; INDOLEACETIC ACID; METFORMIN; UNCLASSIFIED DRUG;

ADULT; AFRICAN AMERICAN; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DETOXIFICATION; DRUG BLOOD LEVEL; DRUG EXPOSURE; DRUG RESPONSE; FEMALE; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN EXPERIMENT; INSULIN RESISTANCE; MALE; MAXIMUM PLASMA CONCENTRATION; METABOLOMICS; MOUSE; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PHARMACOMETABOLOMICS; PROTEIN DEGRADATION; PURINE METABOLISM; UREA CYCLE;

EID: 84977666759     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2016.00135     Document Type: Article

References (47)

1. Atkuri, K. R., Cowan, T. M., Kwan, T., Ng, A., Herzenberg, L. A., Herzenberg, L. A., et al. (2009). Inherited disorders affecting mitochondrial function are associated with glutathione deficiency and hypocitrullinemia. Proc. Natl. Acad. Sci. U.S.A. 106, 3941-3945. doi: 10.1073/pnas.0813409106
2. Bal, F., Bekpinar, S., Unlucerci, Y., Kusku-Kiraz, Z., Önder, S., Uysal, M., et al. (2014). Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in experimental liver injury. Diabetes Res. Clin. Pract. 106, 295-302. doi: 10.1016/j.diabres.2014.08.028
3. Benjamini, Y., and Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B Methodol. 57, 289-300.
4. Cabreiro, F., Au, C., Leung, K.-Y., Vergara-Irigaray, N., Cochemé, H. M., Noori, T., et al. (2013). Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228-239. doi: 10.1016/j.cell.2013.02.035
5. Cai, S., Huo, T., Li, N., Xiong, Z., and Li, F. (2009). Lysophosphatidylcholine-biomarker of etformin action: studied using UPLC/MS/MS. Biomed. Chromatogr. 23, 782-786. doi: 10.1002/bmc.1185
6. Centers for Disease Control Prevention (2014). National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA.
7. Chen, L., Shu, Y., Liang, X., Chen, E. C., Yee, S. W., Zur, A. A., et al. (2014). OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proc. Natl. Acad. Sci. U.S.A. 111, 9983-9988. doi: 10.1073/pnas.1314939111
8. Cho, K., Chung, J. Y., Cho, S. K., Shin, H.-W., Jang, I.-J., Park, J.-W., et al. (2015). Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRa/POMC pathway. Sci. Rep. 5:8145. doi: 10.1038/srep08145
9. Duncan, B. B., and Schmidt, M. I. (2009). Metformin, cancer, alphabet soup, and the role of epidemiology in etiologic research. Diabetes Care 32, 1748-1750. doi: 10.2337/dc09-1183
10. El-Mir, M. Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., and Leverve, X. (2000). Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J. Biol. Chem. 275, 223-228. doi: 10.1074/jbc.275.1.223
11. Evans, J. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., and Morris, A. D. (2005). Metformin and reduced risk of cancer in diabetic patients. BMJ 330, 1304-1305. doi: 10.1136/bmj.38415.708634.F7
12. Ferrannini, E., Natali, A., Camastra, S., Nannipieri, M., Mari, A., Adam, K.-P., et al. (2013). Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance. Diabetes 62, 1730-1737. doi: 10.2337/db12-0707
13. Gall, W. E., Beebe, K., Lawton, K. A., Adam, K.-P., Mitchell, M. W., Nakhle, P. J., et al. (2010). Alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS ONE 5:e10883. doi: 10.1371/journal.pone.0010883
14. Huo, T., Cai, S., Lu, X., Sha, Y., Yu, M., and Li, F. (2009). Metabonomic study of biochemical changes in the serum of type 2 diabetes mellitus patients after the treatment of metformin hydrochloride. J. Pharm. Biomed. Anal. 49, 976-982. doi: 10.1016/j.jpba.2009.01.008
15. Irving, B. A., Carter, R. E., Soop, M., Weymiller, A., Syed, H., Karakelides, H., et al. (2015). Effect of insulin sensitizer therapy on amino acids and their metabolites. Metabolism 64, 720-728. doi: 10.1016/j.metabol.2015.01.008
16. Janzer, A., German, N. J., Gonzalez-Herrera, K. N., Asara, J. M., Haigis, M. C., and Struhl, K. (2014). Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells. Proc. Natl. Acad. Sci. U.S.A. 111, 10574-10579. doi: 10.1073/pnas.1409844111
17. Jenkins, C. L., Bretscher, L. E., Guzei, I. A., and Raines, R. T. (2003). Effect of 3-hydroxyproline residues on collagen stability. J. Am. Chem. Soc. 125, 6422-6427. doi: 10.1021/ja034015j
18. Ji, Y., Hebbring, S., Zhu, H., Jenkins, G. D., Biernacka, J., Snyder, K., et al. (2011). Glycine and a Glycine Dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin. Pharmacol. Ther. 89, 97-104. doi: 10.1038/clpt.2010.250
19. Kaddurah-Daouk, R., Weinshilboum, R. M., and Pharmacometabolomics Research Network (2014). Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology. Clin. Pharmacol. Ther. 95, 154-167. doi: 10.1038/clpt.2013.217
20. Kaddurah-Daouk, R., Weinshilboum, R., and Pharmacometabolomics Research Network (2015). Metabolomic signatures for drug response phenotypes: pharmacometabolomics enables precision medicine. Clin. Pharmacol. Ther. 98, 71-75. doi: 10.1002/cpt.134
21. Kaddurah-Daouk, R., Zhu, H., Sharma, S., Bogdanov, M., Rozen, S. G., Matson, W., et al. (2013). Alterations in metabolic pathways and networks in Alzheimer's disease. Transl. Psychiatry 3, e244. doi: 10.1038/tp.2013.18
22. Kita, Y., Takamura, T., Misu, H., Ota, T., Kurita, S., Takeshita, Y., et al. (2012). Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis. PLoS ONE 7:e43056. doi: 10.1371/journal.pone.0043056
23. Lee, H., and Ko, G. (2014). Effect of metformin on metabolic improvement and gut microbiota. Appl. Environ. Microbiol. 80, 5935-5943. doi: 10.1128/AEM.01357-14
24. Lekshmi, U. M. D., and Reddy, P. N. (2013). Studies on the effect of antidiabetic drugs on collagen in rats. Pak. J. Biol. Sci. PJBS 16, 1545-1550. doi: 10.3923/pjbs.2013.1545.1550
25. Lewis, J. P., Yerges-Armstrong, L. M., Ellero-Simatos, S., Georgiades, A., Kaddurah-Daouk, R., and Hankemeier, T. (2013). Integration of pharmacometabolomic and pharmacogenomics approaches reveals novel insights into antiplatelet therapy. Clin. Pharmacol. Ther. 94, 570-573. doi: 10.1038/clpt.2013.153
26. Liang, X., Chien, H.-C., Yee, S. W., Giacomini, M. M., Chen, E. C., Piao, M., et al. (2015). Metformin is a substrate and inhibitor of the human thiamine transporter, THTR-2 (SLC19A3). Mol. Pharm. 12, 4301-4310. doi: 10.1021/acs.molpharmaceut.5b00501
27. Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X.-M., Braddock, D. T., Albright, R. A., et al. (2014). Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 510, 542-546. doi: 10.1038/nature13270
28. Morris, S. M. (2002). Regulation of enzymes of the urea cycle and arginine metabolism. Annu. Rev. Nutr. 22, 87-105. doi: 10.1146/annurev.nutr.22.110801.140547
29. Muscelli, E., Frascerra, S., Casolaro, A., Baldi, S., Mari, A., Gall, W., et al. (2014). The amino acidresponse to a mixed meal in patients with type 2 diabetes: effect of sitagliptin treatment. Diabetes Obes. Metab. 16, 1140-1147. doi: 10.1111/dom.12350
30. Owen, M. R., Doran, E., and Halestrap, A. P. (2000). Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348(Pt 3), 607-614. doi: 10.1042/bj3480607
31. Pawlyk, A. C., Giacomini, K. M., McKeon, C., Shuldiner, A. R., and Florez, J. C. (2014). Metformin pharmacogenomics: current status and future directions. Diabetes 63, 2590-2599. doi: 10.2337/db13-1367
32. Rabier, D., Diry, C., Rotig, A., Rustin, P., Heron, B., Bardet, J., et al. (1998). Persistent hypocitrullinaemia as a marker for mtDNA NARP T 8993 G mutation? J. Inherit. Metab. Dis. 21, 216-219.
33. R Development Core Team (2014). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna. Available online at: http://www. R-project.org
34. Rotroff, D., Shahin, M. H. A., Gurley, S. B., Zhu, H., Motsinger-Reif, A. A., Meisner, M., et al. (2015). Pharmacometabolomic assessments of atenolol and hydrochlorothiazide treatment reveal novel drug response phenotypes. CPT Pharmacometerics Syst Pharmacol. 4, 669-679. doi: 10.1002/psp4.12017
35. Sahra, I. B., Regazzetti, C., Robert, G., Laurent, K., Marchand-Brustel, Y. L., Auberger, P., et al. (2011). Metformin, Independent of AMPK, Induces mTOR Inhibition and Cell-Cycle Arrest through REDD1. Cancer Res. 71, 4366-4372. doi: 10.1158/0008-5472.CAN-10-1769
36. Song, I.-S., Lee, D. Y., Shin, M.-H., Kim, H., Ahn, Y. G., Park, I., et al. (2012). Pharmacogenetics meets metabolomics: discovery of tryptophan as a new endogenous OCT2 substrate related to metformin disposition. PLoS ONE 7:e36637. doi: 10.1371/journal.pone.0036637
37. Stocker, S. L., Morrissey, K. M., Yee, S. W., Castro, R. A., Xu, L., Dahlin, A., et al. (2013). The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Clin. Pharmacol. Ther. 93, 186-194. doi: 10.1038/clpt.2012.210
38. Stone, E. A., and Ayroles, J. F. (2009). Modulated modularity clustering as an exploratory tool for functional genomic inference. PLoS Genet. 5:e1000479. doi: 10.1371/journal.pgen.1000479
39. Trupp, M., Zhu, H., Wikoff, W. R., Baillie, R. A., Zeng, Z.-B., Karp, P. D., et al. (2012). Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment. PLoS ONE 7:e38386. doi: 10.1371/journal.pone.0038386
40. Wikoff, W. R., Frye, R. F., Zhu, H., Gong, Y., Boyle, S., Churchill, E., et al. (2013). Pharmacometabolomics reveals racial differences in response to atenolol treatment. PLoS ONE 8:e57639. doi: 10.1371/journal.pone.0057639
41. Wishart, D. S., Jewison, T., Guo, A. C., Wilson, M., Knox, C., Liu, Y., et al. (2013). HMDB 3.0-The Human Metabolome Database in 2013. Nucleic Acids Res. 41, D801-D807. doi: 10.1093/nar/gks1065
42. Xu, T., Brandmaier, S., Messias, A. C., Herder, C., Draisma, H. H. M., Demirkan, A., et al. (2015). Effects of metformin on metabolite profiles and LDL cholesterol in patients with Type 2 Diabetes. Diabetes Care 38, 1858-1867. doi: 10.2337/dc15-0658
43. Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., and Pollak, M. (2006). Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66, 10269-10273. doi: 10.1158/0008-5472.CAN-06-1500
44. Zakikhani, M., Dowling, R. J., Sonenberg, N., and Pollak, M. N. (2008). The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prev. Res. (Phila.) 1, 369-375. doi: 10.1158/1940-6207.CAPR-08-0081
45. Zhang, X., Zhao, Y., Xu, J., Xue, Z., Zhang, M., Pang, X., et al. (2015). Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci. Rep. 5:14405. doi: 10.1038/srep14405
46. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., et al. (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174. doi: 10.1172/JCI13505
47. Zhu, H., Bogdanov, M. B., Boyle, S. H., Matson, W., Sharma, S., Matson, S., et al. (2013). Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder-possible role for methoxyindole pathway. PLoS ONE 8:e68283. doi: 10.1371/journal.pone.0068283