Evidence map›Paper›PMID 31703101›Full record

ArticlePloS one2019

Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals.

Monta Briviba, Ivars Silamikelis, Ineta Kalnina, Laura Ansone, Vita Rovite, Ilze Elbere, Ilze Radovica-Spalvina, Davids Fridmanis, Jekaterina Aladyeva, Ilze Konrade and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 24 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Monta BrivibaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ivars SilamikelisLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ineta KalninaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Laura AnsoneLatvian Biomedical Research and Study Centre, Riga, Latvia.
Vita RoviteLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ilze ElbereLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ilze Radovica-SpalvinaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Davids FridmanisLatvian Biomedical Research and Study Centre, Riga, Latvia.
Jekaterina AladyevaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ilze KonradeRiga Stradins University, Riga, Latvia.
Valdis PiragsLatvian Biomedical Research and Study Centre, Riga, Latvia.
Janis KlovinsLatvian Biomedical Research and Study Centre, Riga, Latvia.ORCID 0000-0001-8362-5505
Latvian Biomedical Research and Study Centre · LVRiga Stradiņš University · LV

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Gene Expression ProfilingTranscriptomeAdultBiomarkersBlood CellsClinical Trials as TopicComputational BiologyFecesFemaleGene Expression RegulationHealthy VolunteersHigh-Throughput Nucleotide SequencingHumansMaleMetforminMiddle AgedBiomarkersIgA, secretory receptorMetforminReceptors, Fc

Identifiers

PMID31703101
PMCPMC6839856
OpenAlexW2988234168

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.