Evidence mapPaperPMID 41188482Full record

ArticleCommunications medicine2025

The metformin mediated MAPK signaling pathway influences D-Xylose regulation during diabetic kidney disease therapy.

Dandan Xie, Yongjun Zhu, Sifan Guo, Hao Li, Zhibo Wang, Xian Wang, Ying Cai, Jinxuan Chai, Yan Wang, Zhencai Hu and 5 more

Abstract read
In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
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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

15 authors.

Dandan Xie *International Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Yongjun Zhu *International Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Sifan Guo *International Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Hao Li *International Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Zhibo WangInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Xian WangInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Ying CaiInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.ORCID http://orcid.org/0009-0005-1223-6365
Jinxuan ChaiInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Yan WangInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Zhencai HuInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Shiwei WangInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China.
Lasi ChenInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China. 251849367@qq.com.
Shi QiuInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China. qiushihnyx@163.com.
Yiqiang XieInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China. xieyiqiang@hainmc.edu.cn.
Aihua ZhangInternational Advanced Functional Omics Platform, School of Chinese Medicine, Scientific Experiment Center, Public Research Center, Hainan Medical University, Haikou, China. aihuatcm@163.com.ORCID http://orcid.org/0000-0002-3784-4472

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiabetic kidney disease (DKD) is a major cause of end-stage renal disease. Although metformin is widely prescribed, the mechanisms underlying its renoprotective effects remain incompletely understood.

methodsWe integrated multi-omics approaches-including network pharmacology, phosphoproteomics, and targeted metabolomics-in both db/db mice (male) and human patients. Analyses were performed on blood and kidney tissue from mice and paired blood/urine samples from DKD patients to identify conserved therapeutic targets and metabolic pathways.

resultsMetformin treatment improves glycemic control and renal function (reduced creatinine and urea nitrogen) in DKD mice. Network pharmacology and phosphoproteomic analyses reveal metformin's engagement with the MAPK pathway, specifically through MAPK1 and MAPK3. Targeted metabolomics identifies four carbohydrate metabolites (mannitol, D-arabitol, D-mannose, and D-xylose) associated with DKD risk in humans. Cross-species validation in mice supports D-Xylose as a potential key biomarker for metformin's therapeutic effects in DKD, with proximal tubule bicarbonate reclamation and alanine, aspartate and glutamate metabolism as key metabolic pathways.

conclusionsMetformin alleviates DKD through multi-modal mechanisms, modulating the MAPK signaling pathway and carbohydrate metabolites-notably D-xylose. As far as we are aware, these findings provide new mechanistic insights and suggest potential biomarker-driven strategies for DKD management.

Identifiers

PMID41188482
PMCPMC12586509

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.