ArticleNature medicine2014
Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 127 citations in OpenAlex.
- Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity.The Journal of nutrition · 2022Trial
- Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment.Nutrients · 2020Trial
- Plasma and aqueous humor levels of Maresin-1 in patients with diabetic retinopathy.Scientific reports · 2026Article
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.The Journal of clinical investigation · 2026Article
- Protectin DX alleviates lumbar radicular pain in rats by suppressing RIP3/MLKL-associated necroinflammation through restoration of autophagic function.Frontiers in pharmacology · 2026Article
- Context-dependent Activities of Mitrephorone Link Lipid Redirection, Anti-inflammatory Action, and Ferroptosis Control to Hepatocyte Protection.Theranostics · 2026Article
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- Bioactive lipid mediator class switching regulates myogenic cell progression and muscle regeneration.Nature communications · 2025Article
- Deciphering the Potential Role of Specialized Pro-Resolving Mediators in Obesity-Associated Metabolic Disorders.International journal of molecular sciences · 2024Review
- Role and mechanism of specialized pro-resolving mediators in obesity-associated insulin resistance.Lipids in health and disease · 2024Review
- Article
- Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease.Cell reports · 2023Article
- Protectin DX as a therapeutic strategy against frailty in mice.GeroScience · 2023Article
- Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice.Molecular metabolism · 2023Article
- Alcohol and Skeletal Muscle in Health and Disease.Alcohol research : current reviews · 2023Review
- Modeling human heterogeneity of obesity with diversity outbred mice reveals a fat mass-dependent therapeutic window for resolvin E1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions.Progress in lipid research · 2022Review
- Insights in diabetes: Molecular mechanisms-Protectin DX, an anti-inflammatory and a stimulator of inflammation resolution metabolite of docosahexaenoic acid, protects against the development of streptozotocin-induced type 1 and type 2 diabetes mellitus in male Swiss albino mice.Frontiers in endocrinology · 2022Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We previously demonstrated that low biosynthesis of ω-3 fatty acid-derived proresolution mediators, termed protectins, is associated with an impaired global resolution capacity, inflammation and insulin resistance in obese high-fat diet-fed mice. These findings prompted a more direct study of the therapeutic potential of protectins for the treatment of metabolic disorders. Herein we show that protectin DX (PDX) exerts an unanticipated glucoregulatory activity that is distinct from its anti-inflammatory actions. We found that PDX selectively stimulated the release of the prototypic myokine interleukin-6 (IL-6) from skeletal muscle and thereby initiated a myokine-liver signaling axis, which blunted hepatic glucose production via signal transducer and activator of transcription 3 (STAT3)-mediated transcriptional suppression of the gluconeogenic program. These effects of PDX were abrogated in Il6-null mice. PDX also activated AMP-activated protein kinase (AMPK); however, it did so in an IL-6-independent manner. Notably, we demonstrated that administration of PDX to obese diabetic db/db mice raises skeletal muscle IL-6 levels and substantially improves their insulin sensitivity without any impact on adipose tissue inflammation. Our findings thus support the development of PDX-based selective muscle IL-6 secretagogues as a new class of therapy for the treatment of insulin resistance and type 2 diabetes.
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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.