{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T01:45:11Z","timestamp":1774057511569,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":1859,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Twelve Icelandic horses in various metabolic states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Horses were subjected to 3 oral glucose tests (OGT; 0.5 g\/kg body weight glucose). Basal, 120 and 180\u2009minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis tandem mass spectrometry metabolomic assay. Insulin concentrations were measured using an ELISA. Analysis was performed using linear models and partial least-squares regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The kynurenine : tryptophan ratio increased over time during the OGT (adjusted P-value = .001). A high insulin response was associated with lower arginine (adjusted P-value = .02) and carnitine (adjusted P-value = .03) concentrations. A predictive model using only baseline samples performed well with as few as 7 distinct metabolites (sensitivity, 86%; 95% confidence interval [CI], 81%-90%; specificity, 88%; 95% CI, 84%-92%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Our results suggest induction of low-grade inflammation during the OGT. Plasma arginine and carnitine concentrations were lower in horses with high insulin response and could constitute potential therapeutic targets. Development of screening tools to identify insulin-dysregulated horses using only baseline blood sample appears promising.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.15992","type":"journal-article","created":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T04:16:23Z","timestamp":1607141783000},"page":"597-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Metabolic changes induced by oral glucose tests in horses and their diagnostic use"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-3499","authenticated-orcid":false,"given":"Julien","family":"Delarocque","sequence":"first","affiliation":[{"name":"Clinic for Horses, University of Veterinary Medicine Hannover, Foundation , Hanover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Frers","sequence":"additional","affiliation":[{"name":"Clinic for Horses, University of Veterinary Medicine Hannover, Foundation , Hanover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Feige","sequence":"additional","affiliation":[{"name":"Clinic for Horses, University of Veterinary Medicine Hannover, Foundation , Hanover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Korinna","family":"Huber","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim , Stuttgart,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation , Hanover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-4674","authenticated-orcid":false,"given":"Tobias","family":"Warnken","sequence":"additional","affiliation":[{"name":"Clinic for Horses, University of Veterinary Medicine Hannover, Foundation , Hanover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"issue":"1","key":"2026020922100543000_jvim15992-bib-0001","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1939-1676.2010.0503.x","article-title":"Equine metabolic syndrome","volume":"24","author":"Frank","year":"2010","journal-title":"J Vet Intern Med"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0002","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/evj.12169","article-title":"Insulin dysregulation","volume":"46","author":"Frank","year":"2014","journal-title":"Equine Vet J"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0003","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/jvim.15423","article-title":"ECEIM consensus statement on equine metabolic syndrome","volume":"33","author":"Durham","year":"2019","journal-title":"J Vet Intern Med"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0004","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.tvjl.2007.07.003","article-title":"Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies","volume":"174","author":"Asplin","year":"2007","journal-title":"Vet J"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0005","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2746\/042516409X475779","article-title":"Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses","volume":"42","author":"de Laat","year":"2010","journal-title":"Equine Vet J"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.domaniend.2017.10.008","article-title":"The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates","volume":"63","author":"Meier","year":"2018","journal-title":"Domest Anim Endocrinol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0007","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.vetimm.2012.07.003","article-title":"Novel link between inflammation and impaired glucose transport during equine insulin resistance","volume":"149","author":"Waller","year":"2012","journal-title":"Vet Immunol Immunopathol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0008","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.vetimm.2008.11.004","article-title":"Inflammatory and redox status of ponies with a history of pasture-associated laminitis","volume":"129","author":"Treiber","year":"2009","journal-title":"Vet Immunol Immunopathol"},{"key":"2026020922100543000_jvim15992-bib-0009","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12917-018-1479-z","article-title":"Lower plasma trans-4-hydroxyproline and methionine sulfoxide levels are associated with insulin dysregulation in horses","volume":"14","author":"Ken\u00e9z","year":"2018","journal-title":"BMC Vet Res"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0010","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/evj.12703","article-title":"The diagnosis of equine insulin dysregulation","volume":"49","author":"Bertin","year":"2017","journal-title":"Equine Vet J"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0011","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/jvim.15363","article-title":"Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies","volume":"33","author":"Fitzgerald","year":"2018","journal-title":"J Vet Intern Med"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0012","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.vetimm.2011.05.001","article-title":"Effects of acute hyperinsulinemia on inflammatory proteins in horses","volume":"142","author":"Suagee","year":"2011","journal-title":"Vet Immunol Immunopathol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0013","first-page":"329","article-title":"Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses","volume":"79","author":"Banse","year":"2015","journal-title":"Can J Vet Res"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0014","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.2527\/jas.2006-673","article-title":"Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse","volume":"85","author":"Vick","year":"2007","journal-title":"J Anim Sci"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0015","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.vetimm.2011.11.013","article-title":"Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses","volume":"145","author":"Holbrook","year":"2012","journal-title":"Vet Immunol Immunopathol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0016","first-page":"1","article-title":"A metabolomics approach to characterize phenotypes of metabolic transition from late pregnancy to early lactation in dairy cows","volume":"12","author":"Ken\u00e9z","year":"2016","journal-title":"Metabolomics"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0017","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1111\/jvim.15095","article-title":"Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis","volume":"32","author":"Jacob","year":"2018","journal-title":"J Vet Intern Med"},{"key":"2026020922100543000_jvim15992-bib-0018","article-title":"Recommendations for the diagnosis and treatment of pituitary pars intermedia dysfunction (PPID)","author":"Frank","year":"2015"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0019","first-page":"1291","article-title":"Evaluation of an equine-optimized enzyme-linked immunosorbent assay for serum insulin measurement and stability study of equine serum insulin","volume":"21","author":"\u00d6berg","year":"2011","journal-title":"Comp Clin Path"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0020","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3109\/07853890.2015.1137630","article-title":"Metabolomics in diabetes, a review","volume":"48","author":"Pallares-M\u00e9ndez","year":"2016","journal-title":"Ann Med"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0021","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ceb.2007.06.003","article-title":"Lipids and lipid modifications in the regulation of membrane traffic","volume":"19","author":"Haucke","year":"2007","journal-title":"Curr Opin Cell Biol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0022","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol Rev"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0023","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1021\/pr201017n","article-title":"NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis","volume":"11","author":"Klein","year":"2012","journal-title":"J Proteome Res"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0024","first-page":"1","article-title":"A review of lipidomics of cardiovascular disease highlights the importance of isolating lipoproteins","volume":"10","author":"Ding","year":"2020","journal-title":"Metabolites"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0025","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","article-title":"A comparison of normalization methods for high density oligonucleotide array data based on variance and bias","volume":"19","author":"Bolstad","year":"2003","journal-title":"Bioinformatics"},{"key":"2026020922100543000_jvim15992-bib-0026","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B"},{"key":"2026020922100543000_jvim15992-bib-0027","article-title":"DiscriMiner: Tools of the Trade for Discriminant Analysis","author":"Sanchez","year":"2013"},{"key":"2026020922100543000_jvim15992-bib-0028","article-title":"Prevalence, Risk Factors and Seasonality of Plasma Insulin Concentrations in Normal Horses in Central Ohio","author":"Muno","year":"2009"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0029","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1111\/jvim.12056","article-title":"Adiposity, plasma insulin, leptin, lipids, and oxidative stress in mature light breed horses","volume":"27","author":"Pleasant","year":"2013","journal-title":"J Vet Intern Med"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0030","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/avj.12159","article-title":"Prevalence and risk factors for hyperinsulinaemia in ponies in Queensland, Australia","volume":"92","author":"Morgan","year":"2014","journal-title":"Aust Vet J"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0031","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.2337\/db12-0754","article-title":"Metabolite profiles during oral glucose challenge","volume":"62","author":"Ho","year":"2013","journal-title":"Diabetes"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0032","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/msb.2008.50","article-title":"Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity","volume":"4","author":"Shaham","year":"2008","journal-title":"Mol Syst Biol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0033","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/oby.20491","article-title":"Obesity-related dysregulation of the Tryptophan-Kynurenine metabolism: role of age and parameters of the metabolic syndrome","volume":"22","author":"Mangge","year":"2014","journal-title":"Obesity"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0034","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1210\/endo-123-3-1598","article-title":"Equine Cushing's disease: differential regulation of \u03b2-endorphin processing in tumors of the intermediate pituitary","volume":"123","author":"Millington","year":"1988","journal-title":"Endocrinology"},{"key":"2026020922100543000_jvim15992-bib-0035","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/0021-9681(74)90031-9","article-title":"Glucose intolerance in Parkinson's disease","volume":"27","author":"Lipman","year":"1974","journal-title":"J Chronic Dis"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0036","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.molmed.2013.01.002","article-title":"Shared dysregulated pathways lead to Parkinson's disease and diabetes","volume":"19","author":"Santiago","year":"2013","journal-title":"Trends Mol Med"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0037","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/00006676-199109000-00004","article-title":"Effect of L-DOPA administration on islet monoamine oxidase activity and glucose-induced insulin release in the mouse","volume":"6","author":"Lundquist","year":"1991","journal-title":"Pancreas"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0038","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1210\/jcem-33-5-829","article-title":"Endocrine function and glucose metabolism in patients with Parkinson's disease and their alteration by L-dopa","volume":"33","author":"Boyd","year":"1971","journal-title":"J Clin Endocrinol Metab"},{"key":"2026020922100543000_jvim15992-bib-0039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/805683","article-title":"Investigating potential mechanisms of obesity by metabolomics","volume":"2012","author":"Xie","year":"2012","journal-title":"J Biomed Biotechnol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0040","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1194\/jlr.M043448","article-title":"Obesity and lipid stress inhibit carnitine acetyltransferase activity","volume":"55","author":"Seiler","year":"2014","journal-title":"J Lipid Res"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0041","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1439-0396.2008.00807.x","article-title":"Increased plasma leptin through l-carnitine supplementation is associated with an enhanced glucose tolerance in healthy ponies","volume":"93","author":"Van Weyenberg","year":"2009","journal-title":"J Anim Physiol Anim Nutr"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0042","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1136\/vr.103226","article-title":"Equine metabolic syndrome","volume":"177","author":"Morgan","year":"2015","journal-title":"Vet Rec"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0043","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00726-010-0598-z","article-title":"Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health","volume":"39","author":"McKnight","year":"2010","journal-title":"Amino Acids"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0044","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00228-005-0004-z","article-title":"Effect of L-arginine supplementation on NO production in man","volume":"62","author":"Bode-B\u00f6ger","year":"2006","journal-title":"Eur J Clin Pharmacol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0045","first-page":"1","article-title":"Vascular dysfunction in horses with endocrinopathic laminitis","volume":"11","author":"Morgan","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0046","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1161\/01.ATV.20.9.2032","article-title":"Does ADMA cause endothelial dysfunction?","volume":"20","author":"Cooke","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0047","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S1095-6433(01)00295-1","article-title":"Glucose-dependent insulinotropic polypeptide (GIP) and the enteroinsular axis in equines (Equus caballus)","volume":"129","author":"D\u00fchlmeier","year":"2001","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0048","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1210\/jcem-33-3-409","article-title":"Relationships between intravenous glucose loads, insulin responses and glucose disappearance rate","volume":"33","author":"Lerner","year":"1971","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0049","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.tibtech.2017.03.013","article-title":"Multiplexed point-of-care testing \u2013 xPOCT","volume":"35","author":"Dincer","year":"2017","journal-title":"Trends Biotechnol"},{"issue":"1","key":"2026020922100543000_jvim15992-bib-0050","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Research"}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvim.15992","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvim.15992","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/35\/1\/597\/66650078\/jvim15992.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/35\/1\/597\/66650078\/jvim15992.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:19:11Z","timestamp":1770693551000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/35\/1\/597\/8446817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.15992","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1]]},"published":{"date-parts":[[2021,1,1]]},"assertion":[{"value":"2020-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}