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  • Elbere, IlzeLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)

Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-12-13
  • Springer Science and Business Media LLC,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-372930
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-372930URI
  • https://doi.org/10.1186/s13148-018-0593-xDOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background: Metformin is a widely prescribed antihyperglycemic agent that has been also associated with multiple therapeutic effects in various diseases, including several types of malignancies. There is growing evidence regarding the contribution of the epigenetic mechanisms in reaching metformin's therapeutic goals; however, the effect of metformin on human cells in vivo is not comprehensively studied. The aim of our study was to examine metformin-induced alterations of DNA methylation profiles in white blood cells of healthy volunteers, employing a longitudinal study design.Results: Twelve healthy metformin-naive individuals where enrolled in the study. Genome-wide DNA methylation pattern was estimated at baseline, 10h and 7days after the start of metformin administration. The whole-genome DNA methylation analysis in total revealed 125 differentially methylated CpGs, of which 11 CpGs and their associated genes with the most consistent changes in the DNA methylation profile were selected: POFUT2, CAMKK1, EML3, KIAA1614, UPF1, MUC4, LOC727982, SIX3, ADAM8, SNORD12B, VPS8, and several differentially methylated regions as novel potential epigenetic targets of metformin. The main functions of the majority of top-ranked differentially methylated loci and their representative cell signaling pathways were linked to the well-known metformin therapy targets: regulatory processes of energy homeostasis, inflammatory responses, tumorigenesis, and neurodegenerative diseases.Conclusions: Here we demonstrate for the first time the immediate effect of short-term metformin administration at therapeutic doses on epigenetic regulation in human white blood cells. These findings suggest the DNA methylation process as one of the mechanisms involved in the action of metformin, thereby revealing novel targets and directions of the molecular mechanisms underlying the various beneficial effects of metformin.Trial registrationEU Clinical Trials Register, 2016-001092-74. Registered 23 March 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001092-74/LV.

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  • Silamikelis, IvarsLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Ustinova, MontaLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Kalnina, InetaLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Zaharenko, LindaLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Peculis, RaitisLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Konrade, IlzeRiga East Clin Univ Hosp, 2 Hipokrata St, LV-1038 Riga, Latvia (author)
  • Ciuculete, Diana-MariaUppsala universitet,Funktionell farmakologi(Swepub:uu)diaci119 (author)
  • Zhukovsky, ChristinaUppsala universitet,Funktionell farmakologi(Swepub:uu)chrzh593 (author)
  • Gudra, DitaLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Radovica-Spalvina, IlzeLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Fridmanis, DavidsLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Pirags, ValdisLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Schiöth, Helgi B.Uppsala universitet,Funktionell farmakologi(Swepub:uu)helgschi (author)
  • Klovins, JanisLatvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia (author)
  • Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, LatviaRiga East Clin Univ Hosp, 2 Hipokrata St, LV-1038 Riga, Latvia (creator_code:org_t)

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  • In:Clinical Epigenetics: Springer Science and Business Media LLC101868-70831868-7075

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