Evidence map›Paper›PMID 41183805›Full record

ArticleDiabetes & metabolism journal2026

4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects.

Mengqin Tu, Xiaoli Zou, Xiaozhen Tan, Yijun Liu, Xinxu Ge, Yu Hu, Qiuyue Peng, Linlin Huang, Yan Zeng, Chunxia Jia and 4 more

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In one paragraph

Article in Diabetes & metabolism journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Mengqin Tu *Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Xiaoli Zou *Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Xiaozhen TanDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Yijun LiuDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Xinxu GeExperimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Yu HuDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Qiuyue PengDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Linlin HuangDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Yan ZengDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Chunxia JiaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Man GuoDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Jiao ChenDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Yang LongDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China. longyang0217@swmu.edu.cn.
Yong XuDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China. xywyll@swmu.edu.cn.

Funding

National Natural Science Foundation of China 82171860National Natural Science Foundation of China 82371882National Natural Science Foundation of China 82470854National Natural Science Foundation of China U22A20286Office of Science, Technology, and Talent Work of Luzhou 2021LZXNYD-P02Sichuan Province and Luzhou-Southwest Medical University 2022YFS0617Sichuan Science and Technology Program 2023ZYD0095
6 · The paper itself

Abstract

backgruoundDiabetic foot ulcers are a severe diabetic complication characterized by poor healing. Itaconate, a tricarboxylic acid cycle byproduct, has been shown to improve wound healing. This study investigated the potential of 4-octyl itaconate (4-OI), an esterified derivative of itaconate, to modulate efferocytosis and macrophage pro-resolving function to promote diabetic wound healing.

methodsA diabetic mouse wound model was used. For in vitro analysis, RAW264.7 macrophages and apoptotic Jurkat cells were cocultured under high glucose conditions (HG, 30 mM). To further evaluate the roles of macrophages, monocarboxylate transporter 1 (MCT1), and lactate in 4-OI-promoted diabetic wound healing, we used clodronate-liposomes (CLD-Lipo) to deplete macrophages, AZD3965 as an MCT1 inhibitor, and telmisartan to validate our hypothesis.

resultsIn diabetic mice, impaired clearance of apoptotic neutrophils and persistent M1 activation delayed wound healing. 4-OI improved diabetic wound repair by enhancing efferocytosis, shifting macrophages toward an M2 pro-resolving phenotype, and boosting angiogenesis. 4-OI showed a protective effect mediated by macrophages, while endothelial cells and neutrophils also played synergistic roles in diabetic wound healing. Moreover, 4-OI upregulated MCT1, which, in turn, increased the release of lactate triggered by efferocytosis at the wound site. Lastly, we confirmed that the pro-resolving effects of 4-OI onmacrophage function were mediated by promoting pro-resolving macrophage proliferation and polarization via efferocytosis-induced lactate release and subsequent activation of G protein-coupled receptor 132 (GPR132).

conclusion4-OI promotes diabetic wound healing through macrophage-dependent and macrophage-independent mechanisms. Moreover, the protective effect of 4-OI on macrophages was mediated through MCT1-mediated lactate release triggered by efferocytosis and subsequent GPR 132 activation.

Indexed as

Diabetes Mellitus, ExperimentalMacrophagesSuccinatesWound HealingAnimalsApoptosisCell Cycle ProteinsEfferocytosisHumansJurkat CellsLactic AcidMaleMiceMice, Inbred C57BLMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersCell Cycle ProteinsG2A receptoritaconic acidLactic AcidMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersReceptors, G-Protein-CoupledSuccinatesSymportersDiabetes mellitusEfferocytosisG2A receptorLactatesMacrophagesMonocarboxylate transport protein 1Wound healing

Identifiers

PMID41183805
PMCPMC13366132

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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 OpenQuestion graph.