ArticleThe Journal of biological chemistry2011
Metabolomics reveals attenuation of the SLC6A20 kidney transporter in nonhuman primate and mouse models of type 2 diabetes mellitus.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 78 citations in OpenAlex.
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- Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study.World journal of diabetes · 2024Article
- Novel Activity of Oral Hypoglycemic Agents Linked with Decreased Formation of Tryptophan Metabolite, Kynurenic Acid.Life (Basel, Switzerland) · 2024Article
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- TCA Cycle and Fatty Acids Oxidation Reflect Early Cardiorenal Damage in Normoalbuminuric Subjects with Controlled Hypertension.Antioxidants (Basel, Switzerland) · 2021Article
- Crosstalk between Tryptophan Metabolism via Kynurenine Pathway and Carbohydrate Metabolism in the Context of Cardio-Metabolic Risk-Review.Journal of clinical medicine · 2021Review
- Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms.International journal of molecular sciences · 2020 · on this mapReview
- Rapid Solution-Phase Hydrogen/Deuterium Exchange for Metabolite Compound Identification.Journal of the American Society for Mass Spectrometry · 2019Article
- Optimized GC-MS metabolomics for the analysis of kidney tissue metabolites.Metabolomics : Official journal of the Metabolomic Society · 2018Article
- Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet.Frontiers in pharmacology · 2018Article
- Peripheral Tryptophan - Kynurenine Metabolism Associated with Metabolic Syndrome is Different in Parkinson's and Alzheimer's Diseases.Endocrinology, diabetes and metabolism journal · 2017Article
- Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites.Scientific reports · 2017Article
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- Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity.Scientific reports · 2016Article
- A longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, Callithrix jacchus.Experimental gerontology · 2016Article
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- Feature Selection Methods for Early Predictive Biomarker Discovery Using Untargeted Metabolomic Data.Frontiers in molecular biosciences · 2016Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
To enhance understanding of the metabolic indicators of type 2 diabetes mellitus (T2DM) disease pathogenesis and progression, the urinary metabolomes of well characterized rhesus macaques (normal or spontaneously and naturally diabetic) were examined. High-resolution ultra-performance liquid chromatography coupled with the accurate mass determination of time-of-flight mass spectrometry was used to analyze spot urine samples from normal (n = 10) and T2DM (n = 11) male monkeys. The machine-learning algorithm random forests classified urine samples as either from normal or T2DM monkeys. The metabolites important for developing the classifier were further examined for their biological significance. Random forests models had a misclassification error of less than 5%. Metabolites were identified based on accurate masses (<10 ppm) and confirmed by tandem mass spectrometry of authentic compounds. Urinary compounds significantly increased (p < 0.05) in the T2DM when compared with the normal group included glycine betaine (9-fold), citric acid (2.8-fold), kynurenic acid (1.8-fold), glucose (68-fold), and pipecolic acid (6.5-fold). When compared with the conventional definition of T2DM, the metabolites were also useful in defining the T2DM condition, and the urinary elevations in glycine betaine and pipecolic acid (as well as proline) indicated defective re-absorption in the kidney proximal tubules by SLC6A20, a Na(+)-dependent transporter. The mRNA levels of SLC6A20 were significantly reduced in the kidneys of monkeys with T2DM. These observations were validated in the db/db mouse model of T2DM. This study provides convincing evidence of the power of metabolomics for identifying functional changes at many levels in the omics pipeline.
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