Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals

Monta Ustinova, Ivars Silamikelis, Ineta Kalnina, Laura Ansone, Vita Rovite, Ilze Elbere, Ilze Radovica-Spalvina, Davids Fridmanis, Jekaterina Aladyeva, Ilze Konrade, Valdis Pirags, Janis Klovins

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Metformin 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.

Original languageEnglish
Article numbere0224835
JournalPLoS ONE
Volume14
Issue number11
DOIs
Publication statusPublished - 1 Nov 2019

Field of Science

  • 3.2 Clinical medicine
  • 1.6 Biological sciences

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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