Evidence map›Paper›PMID 41530347›Full record

ArticleCell research2026

Lactate-activated GPR81/FARP1 signaling drives insulin-independent glucose uptake and metabolic control.

Yaxin Niu, Shengmin Hu, Yanfeng Zhang, Jinbao Yang, Jiarui Zhang, Ruiping He, Li Chen, Lin Xu, Hongfang Zhao, Bing Gan and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

18 authors.

Yaxin Niu *State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Shengmin Hu *State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Yanfeng ZhangQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, and Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jinbao YangState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Jiarui ZhangState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Ruiping HeState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Li ChenState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-8685-3466
Lin XuQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, and Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hongfang ZhaoState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Bing GanState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Ruobing RenState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-4517-7216
Ruth J F LoosNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Kobenhavn, Denmark.ORCID http://orcid.org/0000-0002-8532-5087
Haobin YeState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Xingrong DuState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-6427-9600
Tongjin ZhaoState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-6861-3071
Peng LiInnovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.ORCID http://orcid.org/0000-0002-8629-5246
Antonio Vidal-PuigWellcome-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-4220-9577
Linzhang HuangState Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China. Linzhang_huang@fudan.edu.cn.ORCID http://orcid.org/0000-0002-9092-2855

Funding

Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HG011996Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL144969Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R21CA259771National Natural Science Foundation of China (National Science Foundation of China) 32171299National Natural Science Foundation of China (National Science Foundation of China) 32471236
6 · The paper itself

Abstract

Insulin-stimulated glucose uptake is central to global carbohydrate metabolism, yet metabolites that enhance glucose uptake independently of insulin remain undefined. Here, we identify L-lactate as an insulin-independent regulator of glucose uptake that mitigates hyperglycemia. Loss of LDHA in muscle reduces lactate production, impairing glucose homeostasis in mice. By contrast, lactate administration or genetic upregulation of lactate production improves glucose control. Knockout of the lactate receptor GPR81 in skeletal muscle worsens glucose tolerance, whereas its ectopic expression or pharmacological activation enhances carbohydrate metabolism. Mechanistically, GPR81 recruits FARP1 to activate RAC1, promoting GLUT4 translocation independently of insulin signaling. Notably, the expression of LDHA, GPR81, and FARP1 is upregulated after exercise, and GPR81 variants are highly correlated with fasting insulin levels in humans, underscoring the synergy of the GPR81-FARP1-GLUT4 axis with insulin in glucose regulation. Our findings suggest that targeting GPR81 represents a potential insulin-independent strategy for the treatment of hyperglycemia.

Indexed as

GlucoseInsulinLactic AcidReceptors, G-Protein-CoupledAnimalsGlucose Transporter Type 4HumansMaleMiceMice, Inbred C57BLMice, KnockoutMuscle, SkeletalSignal TransductionGlucoseGlucose Transporter Type 4Hcar1 protein, mouseInsulinLactic AcidReceptors, G-Protein-Coupled

Identifiers

PMID41530347
PMCPMC12848121

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.