ArticleJCI insight2017
Involvement of the metabolic sensor GPR81 in cardiovascular control.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- Lactylation at the metabolic-epigenetic interface in cardiovascular diseases: context-dependent mechanisms and translational roadmap.Journal of advanced research · 2026Review
- Lactate Receptor Activation Alleviates Senescence and Preserves Homeostasis of Aged Arteries.bioRxiv : the preprint server for biology · 2026Article
- Lactate as a Cardiovascular Exerkine: Mechanisms, Signaling Pathways, and Clinical Implications.Biomolecules · 2026Review
- From Byproduct to Regulator: The Expanding Role of Lactate and Lactylation in Cardiovascular Physiology and Disease.Biology · 2026Review
- Lactylation formation, gene regulation, biological functions, and clinical relevance.Histology and histopathology · 2026Review
- Lactate and Lactylation in Pulmonary Hypertension: Comprehensive Landscape and Future Perspectives.International journal of medical sciences · 2026Review
- Exercise increases bone mass by lactate/Gpr81 signaling pathway.Communications biology · 2025Article
- The new insights of lactate in various kidney diseases.Expert reviews in molecular medicine · 2025Review
- Lactate Metabolism and Lactylation Modification: New Opportunities and Challenges in Cardiovascular Disease.MedComm · 2025Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
- Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate-Lactylation Perspective.International journal of molecular sciences · 2025Review
- Structures of G-protein coupled receptor HCAR1 in complex with Gi1 protein reveal the mechanistic basis for ligand recognition and agonist selectivity.PLoS biology · 2025Article
- Lactate homeostasis is maintained through regulation of glycolysis and lipolysis.Cell metabolism · 2025Article
- Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.Journal of medicinal chemistry · 2025Article
- Lactate Ameliorates Kainic Acid-Induced Neuroinflammation and Cognitive Impairment via the Chemokine Signaling Pathway in Mice.Journal of inflammation research · 2025Article
- Review
- High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81.Cells · 2024Article
- Lack of HCAR1, the lactate GPCR, signaling promotes autistic-like behavior.Cell communication and signaling : CCS · 2023Article
- Current understanding of the contribution of lactate to the cardiovascular system and its therapeutic relevance.Frontiers in endocrinology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GPR81 is a receptor for the metabolic intermediate lactate with an established role in regulating adipocyte lipolysis. Potentially novel GPR81 agonists were identified that suppressed fasting plasma free fatty acid levels in rodents and in addition improved insulin sensitivity in mouse models of insulin resistance and diabetes. Unexpectedly, the agonists simultaneously induced hypertension in rodents, including wild-type, but not GPR81-deficient mice. Detailed cardiovascular studies in anesthetized dogs showed that the pressor effect was associated with heterogenous effects on vascular resistance among the measured tissues: increasing in the kidney while remaining unchanged in hindlimb and heart. Studies in rats revealed that the pressor effect could be blocked, and the renal resistance effect at least partially blocked, with pharmacological antagonism of endothelin receptors. In situ hybridization localized GPR81 to the microcirculation, notably afferent arterioles of the kidney. In conclusion, these results provide evidence for a potentially novel role of GPR81 agonism in blood pressure control and regulation of renal vascular resistance including modulation of a known vasoeffector mechanism, the endothelin system. In addition, support is provided for the concept of fatty acid lowering as a means of improving insulin sensitivity.
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Registered trials
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.