Evidence map›Paper›PMID 40660708›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

MCT1-mediated Lactate Shuttle to Mitochondria Governs Macrophage Polarization and Modulates Glucose Homeostasis by Affecting β Cells.

Lingling Chen, Yijun Lin, Xinyu Zhu, Shixuan Zhuo, Zixuan Li, Cheng Guo, Xiaoyi Ye, Jinzhu Chen, Shuying Wang, Yan Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Review
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  4. Brain-muscle axis regulation of neuroinflammation and sarcopenia in Parkinson's disease: the bridging role of lactylation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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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

10 authors.

Lingling ChenCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Yijun LinXiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, 361016, China.
Xinyu ZhuSchool of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
Shixuan ZhuoCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Zixuan LiCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Cheng GuoCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Xiaoyi YeCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Jinzhu ChenCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Shuying WangCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Yan ChenCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.ORCID https://orcid.org/0000-0002-6630-0693

Funding

Chronic Non-Communicable Diseases-National Science and Technology Major Project of China 2404ZD0531300National Key Research and Development Program of China 2023YFA1801100National Natural Science Foundation of China 32230047Shanghai Municipal Science and Technology Major Project
6 · The paper itself

Abstract

As a major fuel source for the tricarboxylic acid cycle, lactate controls energy metabolism through cell-to-cell or tissue-to-tissue lactate shuttles via monocarboxylate transporters (MCTs). Although lactate is shown to influence macrophage functions via histone lactylation, the specific functions of MCTs in macrophages remain incompletely understood. This study discovers that MCT1 and MCT4 have contrasting effects on regulating macrophage polarization. M1 polarization is associated with increase of MCT4 while M2 polarization is accompanied with increase of MCT1. MCT1 is mainly localized in mitochondria while MCT4 is localized on the plasma membrane. M1 polarization elevates lactate efflux from the cytoplasm to extracellular space, while M2 polarization increases intracellular lactate flux to mitochondria. At cellular level, blocking MCT1 exacerbates LPS-induced M1-like polarization and impairs mitochondria function. At animal level, deletion of MCT1 in macrophages exacerbates glucose intolerance, suppresses insulin secretion and increases islet cell death in high-fat diet fed mice. Mechanistically, lactate reduces insulin secretion through GPR81-cAMP-PKA signaling pathway. These findings not only disclose that the MCT1-mediated intracellular lactate shuttle to the mitochondria plays a pivotal role in governing macrophage polarization but also uncovers a functional interplay between macrophages and β cells in maintaining glucose homeostasis.

Indexed as

GlucoseInsulin-Secreting CellsLactic AcidMacrophagesMitochondriaMonocarboxylic Acid TransportersSymportersAnimalsHomeostasisMaleMiceMice, Inbred C57BLMonocarboxylate Transport Protein 1GlucoseLactic AcidMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersSymportersglucose homeostasislactate shuttlemacrophageMCT1mitochondriapancreatic islet

Identifiers

PMID40660708
PMCPMC12520533

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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 OpenQuestion graph.