PubMed

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/07/31PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolite changes behind faster growth and less reproduction of Daphnia similis exposed to low-dose silver nanoparticles. Ecotoxicol Environ Saf. 2018 Jul 26;163:266-273 Authors: Wang P, Ng QX, Zhang H, Zhang B, Ong CN, He Y Abstract With increasing presence of silver nanoparticles (AgNPs) into the environment, the chronic and low-dose effects of AgNPs are of vital concern. This study evaluated chronic physiological effects of AgNPs on Daphnia similis, which were exposed to two ambient encountered concentrations (0.02 and 1 ppb) of AgNPs for 21 days. It was observed that the low-dose AgNPs stimulated a significant increase in average length/dry mass, but inhibited reproduction compared to control specimens. Non-targeted metabolomics based on liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-QTOFMS-MS) and gas chromatograph-quadrupole time of flight mass spectrometry (GC-QTOF-MS) were utilized to elucidate the underlying molecular mechanisms of these responses. Forty one metabolites were identified, including 18 significantly-changed metabolites, suggesting up regulation in protein digestion and absorption (amino acids, such as isoleucine, tryptophan, lysine, leucine, valine, aspartic acid, threonine, tyrosine) and down regulation of lipid related metabolism (fatty acids, such as arachidonic acid, stearidonic acid, linoelaidic acid and eicosapentaenoic acid) were key events in these responses. The increase in these amino acid contents explains the accelerated growth of D. similis from the metabolic pathway of aminoacyl-tRNA biosynthesis. Down regulation of fatty acid contents corresponds to the observed drop in the reproduction rate considering the fatty acid biological enzymatic reaction pathways. Significant changes in metabolites provided a renewed mechanistic understanding of low concentration chronic toxicity of AgNP toxicity on D. similis. PMID: 30056340 [PubMed - as supplied by publisher]

Metabolic profiling of the anti-tumor drug regorafenib in mice. J Pharm Biomed Anal. 2018 Jul 20;159:524-535 Authors: Wang YK, Xiao XR, Xu KP, Li F Abstract Regorafenib is a novel tyrosine kinase inhibitor, which has been approved by the United States Food and Drug Administration for the treatment of various tumors. The purpose of the present study was to describe the metabolic map of regorafenib, and investigate its effect on liver function. Mass spectrometry-based metabolomics approach integrated with multiple mass defect filter was used to determine the metabolites of regorafenib in vitro incubation mixtures (human liver microsomes and mouse liver microsomes), serum, urine and feces samples from mice treated with 80 mg/kg regorafenib. Eleven metabolites including four novel metabolites were identified in the present investigation. As halogen substituted drug, reductive defluorination and oxidative dechlorination metabolites of regorafenib were firstly report in present study. By screening using recombinant cytochrome P450 s (CYPs), CYP3A4 was found to be the principal isoforms involved in regorafenib metabolism. The predication with a molecular docking model confirmed that regorafenib had potential to interact with the active sites of CYP3A4, CYP3A5 and CYP2D6. Serum chemistry analysis revealed no evidence of hepatic damage from regorafenib exposure. This study provided a global view of regorafenib metabolism and its potential side-effects. PMID: 30055476 [PubMed - as supplied by publisher]

Impact of tart cherries polyphenols on the human gut microbiota and phenolic metabolites in vitro and in vivo. J Nutr Biochem. 2018 Apr 07;59:160-172 Authors: Mayta-Apaza AC, Pottgen E, De Bodt J, Papp N, Marasini D, Howard L, Abranko L, Van de Wiele T, Lee SO, Carbonero F Abstract Tart cherries have been reported to exert potential health benefits attributed to their specific and abundant polyphenol content. However, there is a need to study the impact and fate of tart cherries polyphenols in the gut microbiota. Here, tart cherries, pure polyphenols (and apricots) were submitted to in vitro bacterial fermentation assays and assessed through 16S rRNA gene sequence sequencing and metabolomics. A short-term (5 days, 8 oz. daily) human dietary intervention study was also conducted for microbiota analyses. Tart cherry concentrate juices were found to contain expected abundances of anthocyanins (cyanidin-glycosylrutinoside) and flavonoids (quercetin-rutinoside) and high amounts of chlorogenic and neochlorogenic acids. Targeted metabolomics confirmed that gut microbes were able to degrade those polyphenols mainly to 4-hydroxyphenylpropionic acids and to lower amounts of epicatechin and 4-hydroxybenzoic acids. Tart cherries were found to induce a large increase of Bacteroides in vitro, likely due to the input of polysaccharides, but prebiotic effect was also suggested by Bifidobacterium increase from chlorogenic acid. In the human study, two distinct and inverse responses to tart cherry consumption were associated with initial levels of Bacteroides. High-Bacteroides individuals responded with a decrease in Bacteroides and Bifidobacterium, and an increase of Lachnospiraceae, Ruminococcus and Collinsella. Low-Bacteroides individuals responded with an increase in Bacteroides or Prevotella and Bifidobacterium, and a decrease of Lachnospiraceae, Ruminococcus and Collinsella. These data confirm that gut microbiota metabolism, in particular the potential existence of different metabotypes, needs to be considered in studies attempting to link tart cherries consumption and health. PMID: 30055451 [PubMed - as supplied by publisher]

Related Articles Integrating -Omics Approaches into Human Population-Based Studies of Prenatal and Early-Life Exposures. Curr Environ Health Rep. 2018 Jul 27;: Authors: Everson TM, Marsit CJ Abstract PURPOSE OF REVIEW: We present the study design and methodological suggestions for population-based studies that integrate molecular -omics data and highlight recent studies that have used such data to examine the potential impacts of prenatal environmental exposures on fetal health. RECENT FINDINGS: Epidemiologic studies have observed numerous relationships between prenatal exposures (smoking, toxic metals, endocrine disruptors) and fetal and early-life molecular profiles, though such investigations have so far been dominated by epigenomic association studies. However, recent transcriptomic, proteomic, and metabolomic studies have demonstrated their promise for the identification of exposure and response biomarkers. Molecular -omics have opened new avenues of research in environmental health that can improve our understanding of disease etiology and contribute to the development of exposure and response biomarkers. Studies that incorporate multiple -omics data from different molecular domains in longitudinally collected samples hold particular promise. PMID: 30054820 [PubMed - as supplied by publisher]

Related Articles Comprehensive organic profiling of biological particles derived from blood. Sci Rep. 2018 Jul 27;8(1):11310 Authors: Wu CY, Martel J, Young JD Abstract Mineral nanoparticles form in physiological and pathological processes occurring in the human body. The calcium phosphate mineral phase of the particles has affinity for proteins and lipids, but the complete profiling of the organic molecules that bind to the particles has not been described in detail. We report here a comprehensive analysis of organic components found in mineralo-organic particles derived from body fluids. Based on biological staining, fluorescent tagging, proteomics and metabolomics, our results indicate that the mineral particles bind to proteins, amino acids, carbohydrates, polysaccharides, phospholipids, fatty acids, DNA and low molecular weight metabolites. These results can be used to study the formation and effects of mineralo-organic particles in biological fluids. PMID: 30054526 [PubMed - in process]

Related Articles Complementary intestinal mucosa and microbiota responses to caloric restriction. Sci Rep. 2018 Jul 27;8(1):11338 Authors: Duszka K, Ellero-Simatos S, Ow GS, Defernez M, Paramalingam E, Tett A, Ying S, König J, Narbad A, Kuznetsov VA, Guillou H, Wahli W Abstract The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR. PMID: 30054525 [PubMed - in process]

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/07/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Impact of pulsed UV-B stress exposure on plant performance: How recovery periods stimulate secondary metabolism while reducing adaptive growth attenuation. Plant Cell Environ. 2018 Jul 26;: Authors: Höll J, Lindner S, Walter H, Joshi D, Poschet G, Pfleger S, Ziegler T, Hell R, Bogs J, Rausch T Abstract Upon continuous stress exposure plants display attenuated metabolic stress responses due to regulatory feedback loops. Here we have tested the hypothesis that pulsed stress exposure with intervening recovery periods should affect these feedback loops, thereby causing increased accumulation of stress-induced metabolites. The response of Arabidopsis plantlets to continuous UV-B exposure (Cuv ) was compared to that of pulsed UV-B exposure (Puv ). The differential responses to Puv versus Cuv were monitored at the level of gene expression and metabolite accumulation, using wild type (WT) and different mutant lines. In comparison to Cuv , Puv increased sinapyl and flavonol (S+F) content, whereas adaptive growth attenuation was reduced. Furthermore, in a myb4 mutant (AtMYB4, repressor-type R2R3-MYB transcription factor) the S+F content was increased only for Cuv , but not beyond the level for Puv observed in WT. These observations and the ability of AtMYB4 to repress AtMYB12/AtMYB111-mediated activation of target gene promoters (pCHS, pFLS) indicate that the increase of S+F content after Puv observed in WT plants results from reduced feedback inhibition by AtMYB4. The results support the notion that stress-induced metabolic changes not necessarily cause a growth penalty. Furthermore, the observed Puv -induced increase in flavonol accumulation may stimulate reevaluation of commercial plant production practices. PMID: 30049021 [PubMed - as supplied by publisher]

1H NMR-based metabolomics of antimalarial plant species traditionally used by Vha-Venda people in Limpopo Province, South Africa and isolation of antiplasmodial compounds. J Ethnopharmacol. 2018 Jul 23;: Authors: Bapela MJ, Heyman H, Senejoux F, Meyer JJM Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The Vha-Venda people living in rural areas of Limpopo Province of South Africa regularly use traditional plant-based medicines to treat malaria. In our earlier publication, twenty indigenous plant species used to treat malaria or its symptoms by Vha-Venda people were evaluated for antiplasmodial activity. The main objective of the current study was to assess the robustness of NMR-based metabolomics in discriminating classes of secondary compounds that are responsible for the observed antimalarial activity and the isolation of antiplasmodial compounds. MATERIALS AND METHODS: Twenty dichloromethane extracts were reconstituted in CDCl3, subjected to 1H NMR-based metabolomic analysis on a Varian 600MHz spectrometer and the acquired 1H NMR spectra were then evaluated collectively using multivariate data analysis (MDA). Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) were used to 'globally' discern antiplasmodial profiles. A contribution plot was then generated from the OPLS-DA scoring plot in an attempt to determine the classes of compounds that are responsible for the observed grouping. Further phytochemical analyses were conducted on the lipophilic extracts of Tabernaemontana elegans and Vangueria infausta subsp. infausta. These best candidates were fractionated, purified and their isolated compounds identified based on conventional chromatographic and spectroscopic techniques. RESULTS: The PCA did not separate the acquired profiles according to the detected antiplasmodial bioactivity. Application of a supervised OPLS-DA on the 1H NMR profiles resulted in a discrimination pattern that could be correlated to the observed antimalarial bioactivity. A contribution plot generated from the OPLS-DA scoring plot illustrated the classes of compounds responsible for the observed grouping. Prominent peaks were observed in the aromatic, sugar-based/N-containing and aliphatic spectral regions of the contribution plot. Two known indole alkaloids were isolated from T. elegans, and identified as tabernaemontanine (IC50 = 12.0±0.8µM) and dregamine (IC50 = 62.0±2.4µM). Friedelin (IC50 = 7.20±0.5µM) and morindolide (IC50 = 107.1±0.6µM) were isolated from V. infausta subsp. infausta. This is the first report of the rare iridoid lactone, morindolide's antimalarial activity. While these two compounds have been previously identified, this is the first account of their occurrence in the genus Vangueria. CONCLUSION: The study illustrated the potential of NMR-based metabolomics in discriminating classes of compounds that may be attributed to antiplasmodial activity. Additionally, the study demonstrated the potential of discovering novel antiplasmodial scaffolds from medicinal plants and the rationale for the bioprospecting antimalarial plant species used by Vha-Venda people. PMID: 30048730 [PubMed - as supplied by publisher]

Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential. Pharmacol Ther. 2018 Jul 23;: Authors: Xiang AS, Meikle PJ, Carey AL, Kingwell BA Abstract Development of therapeutic agents directed towards increasing brown adipose tissue (BAT) energy expenditure to combat obesity and its comorbidities is currently an area of intense research. Both preclinical and clinical studies have suggested a potentially significant role for BAT in regulating whole body energy expenditure as well as glucose and lipid metabolism. Lipids, particularly long chain fatty acids (LCFAs), are recognized as integral substrates in mediating the primary heat-producing functions of BAT, and to date thought to be principally sourced from stored intracellular lipid droplets. While this prior understanding is not disputed, recent evidence has demonstrated the importance of lipids derived from the circulation, including those from dietary sources and from tissue lipolysis, especially white adipose tissue lipolysis. Moreover, recent studies have shed further light on a potential role for BAT as an autocrine, paracrine and endocrine organ, with lipids as key signaling molecules. Advances in metabolomics have enabled high-resolution exploration of biomolecules that may be associated with various physiological processes and potentially pathological states. Such approaches have led to several novel lipid species recently being associated with BAT function and dysfunction. Further exploration of the circulating lipidome will likely reveal additional novel BAT biomarkers that can inform development of BAT-directed therapies. This review will address current progress and new strategies to identify and characterize BAT-associated lipids which may represent both novel activators and/or activity biomarkers with both research and clinical utility. PMID: 30048608 [PubMed - as supplied by publisher]

NMR-Based Metabolomics Approach To Study the Influence of Different Conditions of Water Irrigation and Greenhouse Ventilation on Zucchini Crops. J Agric Food Chem. 2018 Jul 26;: Authors: Abreu AC, Aguilera-Sáez LM, Peña A, García-Valverde M, Marín P, Valera DL, Fernández I Abstract This study describes the approach of 1H NMR metabolomic profiling for the differentiation of zucchini produced under different conditions of water irrigation (desalinated seawater -0.397 dS/m, 0.52 €/m3 vs groundwater -2.36 dS/m, 0.29 €/m3) and ventilation (surface area of the vent openings/greenhouse area was 15.0% for one sector and 9.8% for the other). Overall, 72 extracts of zucchini ( Cucubirta pepo L. cv Victoria) under four different conditions were regularly analyzed during the spring-summer cycle from April to July 2017. We have found that zucchini plants irrigated with desalinated seawater increased the zucchini production yield, presented fruits with higher concentration of glucose, fructose, and vitamin B3, and displayed an increased antioxidant activity. On the contrary, plant groundwater irrigation produced the increment of sucrose level that could rise the sweetness perception of the fruits. Finally, the ventilation variable produced a higher concentration of trigonelline, histidine, and phenylalanine but only on those zucchinis irrigated with groundwater. PMID: 30047728 [PubMed - as supplied by publisher]

Related Articles Visualization and application of amino acid retention coefficients obtained from modeling of peptide retention. J Sep Sci. 2018 Jul 26;: Authors: Mohammed Y, Palmblad M Abstract We introduce a method for data inspection in liquid separations of peptides using amino acid retention coefficients and their relative change across experiments. Our method allows for the direct comparison between actual experimental conditions, regardless of sample content and without the use of internal standards. The modeling uses linear regression of peptide retention time as a function of amino acid composition. We demonstrate the pH-dependency of the model in a control experiment where the pH of the mobile phase was changed in controlled way. We introduce a score to identify the false discovery rate on peptide spectrum match level that corresponds to the set of most robust models, i.e. to maximize the shared agreement between experiments. We demonstrate the method utility in reversed-phase liquid chromatography using 24 datasets with minimal peptide overlap. We apply our method on datasets obtained from a public repository representing various separation designs, including one-dimensional reversed-phase liquid chromatography followed by tandem mass spectrometry, and two-dimensional online strong cation exchange coupled to reversed-phase liquid chromatography followed by tandem mass spectrometry, and highlight new insights. Our method provides a simple yet powerful way to inspect data quality, in particular for multidimensional separations, improving comparability of data at no additional experimental cost. This article is protected by copyright. All rights reserved. PMID: 30047222 [PubMed - as supplied by publisher]

Related Articles Metabolomics of Vibrio cholerae. Methods Mol Biol. 2018;1839:45-51 Authors: Minato Y, Kirkwood JS, Häse CC Abstract Metabolomics is an "omics" approach to quantitatively measure a large set of metabolites. In this chapter, we describe an example method for performing liquid chromatography coupled to mass spectrometry (LC-MS)-based untargeted metabolomics on a cell extract from Vibrio cholerae. PMID: 30047053 [PubMed - in process]

Related Articles Synthesis and physicochemical characterization of (6S)-5-formiminotetrahydrofolate; a reference standard for metabolomics. Org Biomol Chem. 2018 Jul 26;: Authors: Lewin AH, Silinski P, Zhong D, Gilbert A, Mascarella SW, Seltzman HH Abstract The one-carbon carrier of the formate oxidation level derived from the interaction of tetrahydrofolate and formiminoglutamate, which has been tentatively identified as 5-formiminoltetrahydrofolate, has been prepared by chemical synthesis. Treatment of a solution of (6S)-tetrahydrofolate in aqueous base with excess ethyl formimidate in the presence of anti-oxidant under anaerobic conditions afforded a gummy solid which, based on mass spectral analysis, conformed to a monoformimino derivative of tetrahydrofolate. Further physicochemical characterization by validated methods strongly suggested that the product of chemical synthesis was identical to the enzymatically produced material and that it was, in fact, (6S)-5-formiminotetrahydrofolate. Conditions and handling methods toward maintaining the integrity of this highly sensitive compound were identified and are described, as is analytical methodology, useful for research studies using it. PMID: 30046777 [PubMed - as supplied by publisher]

Related Articles Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep. Sci Rep. 2018 Jul 25;8(1):11225 Authors: Bourdon AK, Spano GM, Marshall W, Bellesi M, Tononi G, Serra PA, Baghdoyan HA, Lydic R, Campagna SR, Cirelli C Abstract By identifying endogenous molecules in brain extracellular fluid metabolomics can provide insight into the regulatory mechanisms and functions of sleep. Here we studied how the cortical metabolome changes during sleep, sleep deprivation and spontaneous wakefulness. Mice were implanted with electrodes for chronic sleep/wake recording and with microdialysis probes targeting prefrontal and primary motor cortex. Metabolites were measured using ultra performance liquid chromatography-high resolution mass spectrometry. Sleep/wake changes in metabolites were evaluated using partial least squares discriminant analysis, linear mixed effects model analysis of variance, and machine-learning algorithms. More than 30 known metabolites were reliably detected in most samples. When used by a logistic regression classifier, the profile of these metabolites across sleep, spontaneous wake, and enforced wake was sufficient to assign mice to their correct experimental group (pair-wise) in 80-100% of cases. Eleven of these metabolites showed significantly higher levels in awake than in sleeping mice. Some changes extend previous findings (glutamate, homovanillic acid, lactate, pyruvate, tryptophan, uridine), while others are novel (D-gluconate, N-acetyl-beta-alanine, N-acetylglutamine, orotate, succinate/methylmalonate). The upregulation of the de novo pyrimidine pathway, gluconate shunt and aerobic glycolysis may reflect a wake-dependent need to promote the synthesis of many essential components, from nucleic acids to synaptic membranes. PMID: 30046159 [PubMed - in process]

Related Articles Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018 Jul 25;: Authors: Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A Abstract Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases. PMID: 30046148 [PubMed - as supplied by publisher]

Related Articles Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination. Nature. 2018 Jul 25;: Authors: Hubler Z, Allimuthu D, Bederman I, Elitt MS, Madhavan M, Allan KC, Shick HE, Garrison E, T Karl M, Factor DC, Nevin ZS, Sax JL, Thompson MA, Fedorov Y, Jin J, Wilson WK, Giera M, Bracher F, Miller RH, Tesar PJ, Adams DJ Abstract Regeneration of myelin is mediated by oligodendrocyte progenitor cells-an abundant stem cell population in the central nervous system (CNS) and the principal source of new myelinating oligodendrocytes. Loss of myelin-producing oligodendrocytes in the CNS underlies a number of neurological diseases, including multiple sclerosis and diverse genetic diseases1-3. High-throughput chemical screening approaches have been used to identify small molecules that stimulate the formation of oligodendrocytes from oligodendrocyte progenitor cells and functionally enhance remyelination in vivo4-10. Here we show that a wide range of these pro-myelinating small molecules function not through their canonical targets but by directly inhibiting CYP51, TM7SF2, or EBP, a narrow range of enzymes within the cholesterol biosynthesis pathway. Subsequent accumulation of the 8,9-unsaturated sterol substrates of these enzymes is a key mechanistic node that promotes oligodendrocyte formation, as 8,9-unsaturated sterols are effective when supplied to oligodendrocyte progenitor cells in purified form whereas analogous sterols that lack this structural feature have no effect. Collectively, our results define a unifying sterol-based mechanism of action for most known small-molecule enhancers of oligodendrocyte formation and highlight specific targets to propel the development of optimal remyelinating therapeutics. PMID: 30046109 [PubMed - as supplied by publisher]

Related Articles Trace N-glycans including sulphated species may originate from various plasma glycoproteins and not necessarily IgG. Nat Commun. 2018 Jul 25;9(1):2916 Authors: Lauc G, Vučković F, Bondt A, Pezer M, Wuhrer M PMID: 30046098 [PubMed - in process]

Related Articles Arginine Metabolism Is Altered in Adults with A-β + Ketosis-Prone Diabetes. J Nutr. 2018 02 01;148(2):185-193 Authors: Mulukutla SN, Hsu JW, Gaba R, Bohren KM, Guthikonda A, Iyer D, Ajami NJ, Petrosino JF, Hampe CS, Ram N, Jahoor F, Balasubramanyam A Abstract Background: A-β + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible β cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. Objective: The objective of this study was to determine the relation between gut microbiome and arginine metabolism and the relation between arginine availability and β cell function in KPD patients compared with control participants. Methods: Kinetics of arginine and related metabolites were measured with stable isotope tracers, and insulin secretory responses to arginine and glucose were determined under euglycemic and hyperglycemic conditions in 6 KPD patients and 6 age-, gender-, and body mass index-matched control participants. Glucose potentiation of arginine-induced insulin secretion was performed in a different set of 6 KPD and 3 control participants. Results: Arginine availability was higher in KPD patients during euglycemia [53.5 ± 4.3 (mean ± SEM) compared with 40.3 ± 2.4 μmol · kg lean body mass (LBM)-1 · h-1, P = 0.03] but declined more in response to hyperglycemia (Δ 10.15 ± 2.6 compared with Δ 3.20 ± 1.3 μmol · kg LBM-1 · h-1, P = 0.041). During hyperglycemia, ornithine flux was not different between groups but after an arginine bolus, plasma ornithine AUC trended higher in KPD patients (3360 ± 294 compared with 2584 ± 259 min · μmol · L-1, P = 0.08). In both euglycemia and hyperglycemia, the first-phase insulin responses to glucose stimulation were lower in KPD patients (euglycemic insulin AUC 282 ± 108 compared with 926 ± 257 min · μU · mL-1, P = 0.02; hyperglycemic insulin AUC 358 ± 79 compared with 866 ± 292 min · μU · mL-1, P = 0.05), but exogenous arginine restored first-phase insulin secretion in KPD patients to the level of control participants. Conclusion: Compared with control participants, KPD patients have increased arginine availability in the euglycemic state, indicating a higher requirement. This is compromised during hyperglycemia, with an inadequate supply of arginine to sustain metabolic functions such as insulin secretion. Exogenous arginine administration restores a normal insulin secretory response. PMID: 29490093 [PubMed - indexed for MEDLINE]