{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:27:46Z","timestamp":1788917266506,"version":"build-2803163510"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["K23DK123392"],"award-info":[{"award-number":["K23DK123392"]}]},{"DOI":"10.13039\/100020526","name":"Vanderbilt Diabetes Research and Training Center","doi-asserted-by":"crossref","award":["DK020593"],"award-info":[{"award-number":["DK020593"]}],"id":[{"id":"10.13039\/100020526","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JDRF Career Development Award","award":["5-ECR-2020-950-A-N"],"award-info":[{"award-number":["5-ECR-2020-950-A-N"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health","award":["R01DK018243"],"award-info":[{"award-number":["R01DK018243"]}]},{"name":"Fractyl Health and Metavention"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and \u03b2-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the \u03b2-cell\u2019s capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.<\/jats:p>","DOI":"10.1371\/journal.pone.0296400","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T18:34:46Z","timestamp":1703270086000},"page":"e0296400","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["A high-fat and fructose diet in dogs mirrors insulin resistance and \u03b2-cell dysfunction characteristic of impaired glucose tolerance in humans"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-0062","authenticated-orcid":true,"given":"Justin M.","family":"Gregory","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Slaughter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie F.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon R.","family":"Hastings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale S.","family":"Edgerton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"Cherrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"pone.0296400.ref001","author":"International Diabetes Federation","year":"2021","journal-title":"IDF Diabetes Atlas, 10th edn."},{"issue":"2","key":"pone.0296400.ref002","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1210\/er.2017-00253","article-title":"The Science of Obesity Management: An Endocrine Society Scientific Statement","volume":"39","author":"GA Bray","year":"2018","journal-title":"Endocr Rev"},{"key":"pone.0296400.ref003","first-page":"1","article-title":"Human disease models in drug development","author":"A Loewa","year":"2023","journal-title":"Nat Rev Bioeng"},{"issue":"3740","key":"pone.0296400.ref004","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1126\/science.153.3740.1127","article-title":"Diabetes, a new mutation in the mouse","volume":"153","author":"KP Hummel","year":"1966","journal-title":"Science"},{"issue":"9","key":"pone.0296400.ref005","article-title":"Obesity-Associated Cancers: Evidence from Studies in Mouse Models.","volume":"11","author":"H. 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