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In pilot studies (3 dogs that had consumed HFFD for 3 yr), 8 wk of daily treatment with fumagillin reduced food intake 29%, weight 6%, and the glycemic excursion during an oral glucose tolerance test (OGTT) 44%. A second group of dogs consumed the HFFD for 17 wk: pretreatment ( weeks 0\u20134), treatment with fumagillin (FUM; n = 6), or no drug (Control, n = 8) ( weeks 4\u201312), washout period ( weeks 12\u201316), and fumagillin or no drug for 1 wk ( week 17). OGTTs were performed at 0, 4, 11, and 16 wk. A hyperinsulinemic hyperglycemic clamp was performed in week 12; 4 chow-fed dogs underwent identical clamps. Kilocalories per day intake during the treatment period was 2,067\u2009\u00b1\u200950 (Control) versus 1,824\u2009\u00b1\u2009202 (FUM). Body weights (kg) increased 1.9\u2009\u00b1\u20090.3 vs. 2.7\u2009\u00b1\u20090.8 (0\u20134 wk) and 1.2\u2009\u00b1\u20090.2 vs. \u22120.02\u2009\u00b1\u20090.9 (4\u201312 wk) in Control versus fumagillin. The OGTT glycemic response was 30% greater in Control versus fumagillin at 11 wk. Net hepatic glucose uptake (NHGU; mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>) in the Chow, Control, and fumagillin dogs was ~1.5\u2009\u00b1\u20090.6, \u22120.1\u2009\u00b1\u20090.1, and 0.3\u2009\u00b1\u20090.4 (with no portal glucose infusion) and 3.1\u2009\u00b1\u20090.6, 0.5\u2009\u00b1\u20090.3, and 1.5\u2009\u00b1\u20090.5 (portal glucose infusion at 4 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>), respectively. Fumagillin improved glucose tolerance and NHGU in HFFD dogs, suggesting methionine aminopeptidase 2 (MetAP2) inhibitors have the potential for improving glycemic control in prediabetes and diabetes. <\/jats:p>","DOI":"10.1152\/ajpendo.00451.2019","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T20:30:59Z","timestamp":1580243459000},"page":"E514-E524","source":"Crossref","is-referenced-by-count":4,"title":["MetAP2 inhibitor treatment of high-fat and -fructose-fed dogs: impact on the response to oral glucose ingestion and a hyperinsulinemic hyperglycemic clamp"],"prefix":"10.1152","volume":"318","author":[{"given":"Mary Courtney","family":"Moore","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie C.","family":"Coate","sequence":"additional","affiliation":[{"name":"Diabetes 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