ReviewMolecular neurobiology2013
Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways.
Review in Molecular neurobiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 5 of them syntheses that pooled it.
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Who cites it
151 citing papers in PubMed, 5 syntheses or guidelines pooled it, 246 citations in OpenAlex.
- The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years.Journal of proteome research · 2025Pooled it
- Metabolomics in Depression: What We Learn from Preclinical and Clinical Evidences.Molecular neurobiology · 2025Pooled it
- Research Progress on the Relationship between Vitamins and Diabetes: Systematic Review.International journal of molecular sciences · 2023Pooled it
- Meta-analysis of NAD(P)(H) quantification results exhibits variability across mammalian tissues.Scientific reports · 2023Pooled it
- Fluorine-18-Labeled PET Radiotracers for Imaging Tryptophan Uptake and Metabolism: a Systematic Review.Molecular imaging and biology · 2020Pooled it
- Assessing pyridoxine adjuvant therapy effects on blood glucose levels in type 2 diabetes: A randomized clinical trial.Journal of medicine and life · 2023 · on this mapTrial
- Article
- D-Psicose Attenuates Hepatic Steatosis and Inflammatory Injury in HFD/STZ-Induced T2DM Mice and Is Associated With Alterations in Gut Microbiota, Tryptophan Metabolism, and Hepatic AhR-Related Signaling.Food science & nutrition · 2026Article
- Tryptophan Metabolism in Digestive and Extra-Digestive Diseases: Mechanisms, Clinical Implications, and Therapeutic Perspectives.Nutrients · 2026Review
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes.International journal of molecular sciences · 2026Review
- The placental tryptophan pathway across gestation: implications for pregnancy outcomes.Human reproduction update · 2026Review
- Tryptophan metabolism in glaucomatous optic neuropathy: from metabolic dysregulation to therapeutic opportunities.Journal of translational medicine · 2026Review
- Serum metabolomics of diabetic dogs treated with daily administration of a commercially available lyophilized feces preparation.Veterinary research communications · 2026Article
- Physical Activity, Metabolic Dysfunction, and the Kynurenine Pathway in Endometriosis and Polycystic Ovary Syndrome: A Literature Review.Biomolecules · 2026Review
- Metformin and Sitagliptin Impact the Brain Kynurenine Pathway: Region-Specific Modulation of Neuroactive Metabolites in Non-Diabetic Male Rats.Molecules (Basel, Switzerland) · 2026Article
- Timing of NAD Deficiency During Organogenesis Dictates Defect Type and Penetrance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hypoxia-Induced Gut-Brain Axis Remodeling and Insomnia: Mechanisms and Microbiota Adaptive Regulation from a Translational Perspective.Journal of inflammation research · 2026Review
- Gut Microbiota Modulation by Abelmoschus manihot (L.) Improves Circulating Metabolites and Alleviates Diabetic Nephropathy in db/db Mice.BioMed research international · 2026Article
- Metabolic reprogramming in placenta and umbilical cord serum of polycystic ovary syndrome pregnancies: testosterone-associated alterations and interaction with obesity.Human reproduction open · 2026Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Insulin resistance (IR) underlines aging and aging-associated medical (diabetes, obesity, dyslipidemia, hypertension) and psychiatric (depression, cognitive decline) disorders. Molecular mechanisms of IR in genetically or metabolically predisposed individuals remain uncertain. Current review of the literature and our data presents the evidences that dysregulation of tryptophan (TRP)-kynurenine (KYN) and KYN-nicotinamide adenine dinucleotide (NAD) metabolic pathways is one of the mechanisms of IR. The first and rate-limiting step of TRP-KYN pathway is regulated by enzymes inducible by pro-inflammatory factors and/or stress hormones. The key enzymes of KYN-NAD pathway require pyridoxal-5-phosphate (P5P), an active form of vitamin B6, as a cofactor. Deficiency of P5P diverts KYN-NAD metabolism from production of NAD to the excessive formation of xanthurenic acid (XA). Human and experimental studies suggested that XA and some other KYN metabolites might impair production, release, and biological activity of insulin. We propose that one of the mechanisms of IR is inflammation- and/or stress-induced upregulation of TRP-KYN metabolism in combination with P5P deficiency-induced diversion of KYN-NAD metabolism towards formation of XA and other KYN derivatives affecting insulin activity. Monitoring of KYN/P5P status and formation of XA might help to identify subjects at risk for IR. Pharmacological regulation of the TRP-KYN and KYN-NAD pathways and maintaining of adequate vitamin B6 status might contribute to prevention and treatment of IR in conditions associated with inflammation/stress-induced excessive production of KYN and deficiency of vitamin B6, e.g., type 2 diabetes, obesity, cardiovascular diseases, aging, menopause, pregnancy, and hepatitis C virus infection.
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