Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals

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dc.contributor.authorUstinova, Monta
dc.contributor.authorSilamikelis, Ivars
dc.contributor.authorKalnina, Ineta
dc.contributor.authorAnsone, Laura
dc.contributor.authorRovite, Vita
dc.contributor.authorElbere, Ilze
dc.contributor.authorRadovica-Spalvina, Ilze
dc.contributor.authorFridmanis, Davids
dc.contributor.authorAladyeva, Jekaterina
dc.contributor.authorKonrade, Ilze
dc.contributor.authorPirags, Valdis
dc.contributor.authorKlovins, Janis
dc.contributor.institutionRīga Stradiņš University
dc.date.accessioned2021-04-12T12:30:04Z
dc.date.available2021-04-12T12:30:04Z
dc.date.issued2019-11-01
dc.descriptionFunding Information: The study was supported by the European Regional Development Fund under the project ?Investigation of interplay between multiple determinants influencing response to metformin: search for reliable predictors for efficacy of type 2 diabetes therapy? (Project No.: 1.1.1.1/16/A/091, https://ec.europa.eu/regional_policy/en/funding/ erdf/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all the volunteers for their participation and acknowledge the Genome Database of the Latvian Population for providing biological material and data. Publisher Copyright: © 2019 Ustinova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.abstractMetformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes mellitus. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response. Next generation sequencing-based transcriptome analysis revealed metformin-induced differential expression of genes involved in intestinal immune network for IgA production and cytokine-cytokine receptor interaction pathways. Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin’s action. In addition to universal effects, 4 clusters of functionally related genes with a subject-specific differential expression were distinguished, including genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). This inter-individual variation of the metformin effect on the transcriptional regulation goes in line with well-known variability of the therapeutic response to the drug.en
dc.description.statusPeer reviewed
dc.format.extent1575318
dc.identifier.citationUstinova, M, Silamikelis, I, Kalnina, I, Ansone, L, Rovite, V, Elbere, I, Radovica-Spalvina, I, Fridmanis, D, Aladyeva, J, Konrade, I, Pirags, V & Klovins, J 2019, 'Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals', PLoS ONE, vol. 14, no. 11, e0224835. https://doi.org/10.1371/journal.pone.0224835
dc.identifier.doi10.1371/journal.pone.0224835
dc.identifier.issn1932-6203
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/3764
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85074700839&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofPLoS ONE
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.2 Clinical medicine
dc.subject1.6 Biological sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Agricultural and Biological Sciences
dc.subjectGeneral
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMetformin strongly affects transcriptome of peripheral blood cells in healthy individualsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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