{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:37:12Z","timestamp":1790987832628,"version":"4.1.0"},"reference-count":40,"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":764,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001655","name":"Grayson Jockey Club Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001655","name":"GJCRF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>5\u2032-adenosine monophosphate-activated protein kinase (AMPK) agonists, particularly resveratrol (RES), have not been extensively evaluated for their effect on insulin dysregulation (ID) in horses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Evaluate the effects of treatment with RES (10\u2009mg\/kg PO q12h), metformin (MET; 30\u2009mg\/kg PO q12h), and aspirin (ASP; 20\u2009mg\/kg PO q24h) on experimentally induced ID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Thirty-three healthy, adult, light-breed horses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Unblinded, placebo-controlled, experimental trial evaluating effects of AMPK agonists (RES, MET, and ASP) on experimentally induced ID. Horses were randomly assigned to a treatment group (RES, MET\/ASP, RES\/ASP, RES\/MET\/ASP, or placebo [CON]) after induction of ID with dexamethasone (0.08\u2009mg\/kg PO q24h for 7\u2009days). Frequently sampled insulin-modified IV glucose tolerance tests (FSIGTT) and oral sugar tests (OST) were performed at baseline, 7\u2009days after ID, and ID plus 7\u2009days of treatment. Minimal model and OST variables were compared between (1-way ANOVA) and within (1-way ANOVA for repeated measures) groups over time to determine effects of treatment on ID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Administration of dexamethasone for 14\u2009days resulted in significantly altered insulin and glucose dynamics (SI, DI, basal [glucose], and [insulin]) and produced clinical signs of laminitis in 5 out of 33 (15%) of horses included in the study. Combination therapy with RES, MET, and ASP did not significantly improve insulin and glucose dynamics in horses with experimentally induced ID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Metabolic testing before glucocorticoid administration should be considered in horses with clinical signs of metabolic syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.16970","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T05:45:16Z","timestamp":1702446316000},"page":"102-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of 5\u2032-adenosine monophosphate-activated protein kinase agonists on insulin and glucose dynamics in experimentally induced insulin dysregulation in horses"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9194-7032","authenticated-orcid":false,"given":"Erin F.","family":"Pinnell","sequence":"first","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]},{"name":"Washington State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Pullman, Washington,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D.","family":"Hostnik","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauria R.","family":"Watts","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-0354","authenticated-orcid":false,"given":"Kathryn J.","family":"Timko","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison A.","family":"Thriffiley","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes R.","family":"Stover","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Koenig","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia M.","family":"Gorman","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9063-540X","authenticated-orcid":false,"given":"Ramiro E.","family":"Toribio","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9716-3452","authenticated-orcid":false,"given":"Teresa A.","family":"Burns","sequence":"additional","affiliation":[{"name":"The Ohio State University College of Veterinary Medicine Department of Veterinary Clinical Sciences, , Columbus, Ohio,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,1]]},"reference":[{"key":"2026020304063072000_jvim16970-bib-0001","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"},{"key":"2026020304063072000_jvim16970-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"},{"key":"2026020304063072000_jvim16970-bib-0003","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"},{"key":"2026020304063072000_jvim16970-bib-0004","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"},{"key":"2026020304063072000_jvim16970-bib-0005","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2460\/ajvr.70.5.665","article-title":"Pharmacokinetics and bioavailability of metformin in horses","volume":"70","author":"Hustace","year":"2009","journal-title":"Am J Vet Res"},{"key":"2026020304063072000_jvim16970-bib-0006","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2460\/ajvr.71.10.1201","article-title":"Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies","volume":"71","author":"Tinworth","year":"2010","journal-title":"Am J Vet Res"},{"key":"2026020304063072000_jvim16970-bib-0007","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/evj.12068","article-title":"Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses","volume":"45","author":"Rendle","year":"2013","journal-title":"Equine Vet J"},{"key":"2026020304063072000_jvim16970-bib-0008","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2746\/042516408X273648","article-title":"The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance","volume":"40","author":"Durham","year":"2008","journal-title":"Equine Vet J"},{"key":"2026020304063072000_jvim16970-bib-0009","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.tvjl.2011.01.015","article-title":"The effect of oral metformin on insulin sensitivity in insulin-resistant ponies","volume":"191","author":"Tinworth","year":"2012","journal-title":"Vet J"},{"key":"2026020304063072000_jvim16970-bib-0010","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1042\/BJ20150125","article-title":"Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity","volume":"468","author":"Ford","year":"2015","journal-title":"Biochem J"},{"key":"2026020304063072000_jvim16970-bib-0011","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1172\/JCI67227","article-title":"AMPK, insulin resistance, and the metabolic syndrome","volume":"123","author":"Ruderman","year":"2013","journal-title":"J Clin Invest"},{"key":"2026020304063072000_jvim16970-bib-0012","doi-asserted-by":"crossref","first-page":"522","DOI":"10.3389\/fendo.2018.00522","article-title":"Real talk: the inter-play between the mTOR, AMPK, and hexosamine biosynthetic pathways in cell signaling","volume":"9","author":"Cork","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026020304063072000_jvim16970-bib-0013","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1111\/jvim.12356","article-title":"Effect of dietary nonstructural carbohydrate content on activation of 5\u2032-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies","volume":"28","author":"Burns","year":"2014","journal-title":"J Vet Intern Med"},{"key":"2026020304063072000_jvim16970-bib-0014","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2165\/00003495-199549050-00007","article-title":"Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus","volume":"49","author":"Dunn","year":"1995","journal-title":"Drugs"},{"key":"2026020304063072000_jvim16970-bib-0015","doi-asserted-by":"crossref","first-page":"489","DOI":"10.2337\/diacare.24.3.489","article-title":"Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects","volume":"24","author":"Mannucci","year":"2001","journal-title":"Diabetes Care"},{"key":"2026020304063072000_jvim16970-bib-0016","doi-asserted-by":"crossref","first-page":"E1205","DOI":"10.1152\/ajpendo.00313.2009","article-title":"The effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and beta-cell dysfunction in overweight and obese nondiabetic men","volume":"297","author":"Xiao","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2026020304063072000_jvim16970-bib-0017","doi-asserted-by":"crossref","first-page":"17272","DOI":"10.1073\/pnas.0608531103","article-title":"AMP-activated protein kinase regulates the assembly of epithelial tight junctions","volume":"103","author":"Zhang","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026020304063072000_jvim16970-bib-0018","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20030535","article-title":"The effects of resveratrol in the treatment of metabolic syndrome","volume":"20","author":"Hou","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026020304063072000_jvim16970-bib-0019","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/nyas.12829","article-title":"Resveratrol as a novel treatment for diseases with mTOR pathway hyperactivation","volume":"1348","author":"Alayev","year":"2015","journal-title":"Ann N Y Acad Sci"},{"key":"2026020304063072000_jvim16970-bib-0020","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/evj.12663","article-title":"Lamellar events related to insulin-like growth factor-1 receptor signalling in two models relevant to endocrinopathic laminitis","volume":"49","author":"Lane","year":"2017","journal-title":"Equine Vet J"},{"key":"2026020304063072000_jvim16970-bib-0021","first-page":"617","article-title":"Diagnostic evaluation of insulin and glucose dynamics in light-breed horses receiving dexamethasone","volume":"63","author":"Timko","year":"2022","journal-title":"Can Vet J"},{"key":"2026020304063072000_jvim16970-bib-0022","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/evj.12242","article-title":"Recovery of insulin sensitivity in mature horses after a 3 week course of dexamethasone therapy","volume":"46","author":"Brennan","year":"2014","journal-title":"Equine Vet J"},{"key":"2026020304063072000_jvim16970-bib-0023","doi-asserted-by":"crossref","first-page":"753","DOI":"10.2460\/ajvr.68.7.753","article-title":"Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses","volume":"68","author":"Tiley","year":"2007","journal-title":"Am J Vet Res"},{"key":"2026020304063072000_jvim16970-bib-0024","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13028-016-0246-z","article-title":"A modified oral sugar test for evaluation of insulin and glucose dynamics in horses","volume":"58","author":"Lindase","year":"2016","journal-title":"Acta Vet Scand"},{"key":"2026020304063072000_jvim16970-bib-0025","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1939-1676.2010.0481.x","article-title":"Evaluation of a veterinary glucometer for use in horses","volume":"24","author":"Hackett","year":"2010","journal-title":"J Vet Intern Med"},{"key":"2026020304063072000_jvim16970-bib-0026","doi-asserted-by":"crossref","DOI":"10.1136\/vr.105607","article-title":"Comparison of a continuous indwelling glucometer with a point-of-care device in healthy adult horses","volume":"187","author":"Cunneen","year":"2020","journal-title":"Vet Rec"},{"key":"2026020304063072000_jvim16970-bib-0027","doi-asserted-by":"crossref","first-page":"844","DOI":"10.2746\/042516409X439661","article-title":"Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses","volume":"41","author":"Toth","year":"2009","journal-title":"Equine Vet J"},{"key":"2026020304063072000_jvim16970-bib-0028","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1111\/jvim.15641","article-title":"Enteroinsular axis response to carbohydrates and fasting in healthy newborn foals","volume":"33","author":"Rings","year":"2019","journal-title":"J Vet Intern Med"},{"key":"2026020304063072000_jvim16970-bib-0029","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0749-0739(02)00015-9","article-title":"Glucocorticoids and laminitis in the horse","volume":"18","author":"Johnson","year":"2002","journal-title":"Vet Clin North Am Equine Pract"},{"key":"2026020304063072000_jvim16970-bib-0030","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.domaniend.2013.11.001","article-title":"Breed differences in insulin sensitivity and insulinemic responses to oral glucose in horses and ponies of moderate body condition score","volume":"47","author":"Bamford","year":"2014","journal-title":"Domest Anim Endocrinol"},{"key":"2026020304063072000_jvim16970-bib-0031","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/evj.13053","article-title":"Heritability of metabolic traits associated with equine metabolic syndrome in welsh ponies and Morgan horses","volume":"51","author":"Norton","year":"2019","journal-title":"Equine Vet J"},{"key":"2026020304063072000_jvim16970-bib-0032","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1111\/jvim.15497","article-title":"Incidence and risk factors for recurrence of endocrinopathic laminitis in horses","volume":"33","author":"de Laat","year":"2019","journal-title":"J Vet Intern Med"},{"key":"2026020304063072000_jvim16970-bib-0033","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1111\/jvim.15419","article-title":"Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis","volume":"33","author":"de Laat","year":"2019","journal-title":"J Vet Intern Med"},{"key":"2026020304063072000_jvim16970-bib-0034","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3945\/ajcn.115.122937","article-title":"Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial","volume":"104","author":"Most","year":"2016","journal-title":"Am J Clin Nutr"},{"key":"2026020304063072000_jvim16970-bib-0035","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.nutres.2012.06.003","article-title":"Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus","volume":"32","author":"Bhatt","year":"2012","journal-title":"Nutr Res"},{"key":"2026020304063072000_jvim16970-bib-0036","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/ptr.5737","article-title":"The impact of resveratrol supplementation on blood glucose, insulin, insulin resistance, triglyceride, and periodontal markers in type 2 diabetic patients with chronic periodontitis","volume":"31","author":"Zare Javid","year":"2017","journal-title":"Phytother Res"},{"key":"2026020304063072000_jvim16970-bib-0037","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2019.117212","article-title":"Resveratrol ameliorates metabolic disorders and insulin resistance in high-fat diet-fed mice","volume":"242","author":"Gong","year":"2020","journal-title":"Life Sci"},{"key":"2026020304063072000_jvim16970-bib-0038","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109767","article-title":"A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications","volume":"125","author":"Huang","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"2026020304063072000_jvim16970-bib-0039","article-title":"Investigation of the effects of a dietary supplement on insulin and adipokine concentrations in equine metabolic syndrome\/insulin dysregulation","volume":"88","author":"Manfredi","year":"2020","journal-title":"J Equine Vet"},{"issue":"1","key":"2026020304063072000_jvim16970-bib-0040","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.2460\/ajvr.2005.66.2114","article-title":"Use of proxies and quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses","volume":"66","author":"Treiber","year":"2005","journal-title":"Am J Vet Res"}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/38\/1\/102\/66662526\/jvim16970.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/38\/1\/102\/66662526\/jvim16970.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:06:42Z","timestamp":1770109602000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/38\/1\/102\/8448573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.16970","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2024,1,1]]},"assertion":[{"value":"2023-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}