Evidence map›Paper›PMID 42653207›Full record

ArticleInternational journal of molecular sciences2026

Analysis of Allele-Specific Expression Highlights Novel Participants of Empagliflozin-Driven Effects on T2DM-Associated Regulatory Pathways.

Elena E Korbolina, Maria Gubina, Leonid O Bryzgalov, Arina O Degtyareva, Anastasia A Evseenko, Elena V Antonseva, Anton I Korbut, Elena Y Rykova, Vadim V Klimontov, Julia G Kzhyshkowska and 1 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Elena E KorbolinaInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Maria GubinaInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.ORCID 0009-0000-2132-3827
Leonid O BryzgalovInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Arina O DegtyarevaInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Anastasia A EvseenkoInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Elena V AntonsevaInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Anton I KorbutInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.ORCID 0000-0003-3502-5892
Elena Y RykovaInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Vadim V KlimontovInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.ORCID 0000-0002-5407-8722
Julia G KzhyshkowskaLaboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 634050 Tomsk, Russia.ORCID 0000-0003-0898-3075
Tatiana I MerkulovaInstitute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.

Funding

The Ministry of Education and Science of the Russian Federation FWNR-2026-0025
6 · The paper itself

Abstract

It is well-known that the morbidity and clinical burden of type 2 diabetes mellitus (T2DM) are predominantly associated with its chronic complications, in which fibrosis is a significant contributor. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have made a pivotal advancement in the therapeutic landscape not only improving glycemic control, but also demonstrating high effectiveness in the prevention and treatment of T2DM complications. In this work, we aimed to assess the transcription factors (TFs) mediating the effects of SGLT2 inhibitor empagliflozin (EMPA) treatment by a comprehensive analysis of the allele-specific expression (ASE) events utilizing the RNA-seq data. Initial logistic regression analysis of the in vitro transcriptomic data for EMPA-treated peripheral blood mononuclear cells (PBMCs) of three healthy donors revealed a significant inter-individual variation in ASE for 240 genes linked to EMPA treatment beyond the glucose-lowering effects. Then, 146 TFs were predicted to regulate the expression of the corresponding targets using motifbreakR and DESeq2. Among these, multiple TFs (including ATF3, ATF4, E2F1, EGR1, FOS, JUN, JUNB, IRF8, KLF6, KLF11, SNAI1, TWIST1, and ZEB1) were involved in the TGF-β/SMAD3 canonical profibrotic signaling cascade, pertinent to diabetes-related fibrosis, playing a significant role in the development of diabetic complications. Further analysis of the in vivo data for the PBMCs from ten T2DM patients initiating EMPA therapy identified 98 TFs related to the ASE variation in both in vitro and in vivo cohorts. To conclude, our integrative allele-specific approach enables the prediction of novel EMPA-responsive regulatory interactions and suggests the important mediators of the mechanisms underlying the effects of EMPA on human PBMCs.

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2Gene Expression RegulationGlucosidesSodium-Glucose Transporter 2 InhibitorsAllelesFemaleHumansLeukocytes, MononuclearMaleSignal TransductionTranscription FactorsTranscriptomeBenzhydryl CompoundsempagliflozinGlucosidesSodium-Glucose Transporter 2 InhibitorsTranscription Factorsallele-specific expressionperipheral blood mononuclear cellsregulatory interactionsresponse to therapyRNA-seqsodium–glucose cotransporter 2 inhibitor empagliflozintranscription factorstype 2 diabetes mellitus

Identifiers

PMID42653207
PMCPMC13513580

What Socratic holds

Textmetadata
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 Socratic graph.