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Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P &amp;lt; 0.05) in (Pro3)GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P &amp;lt; 0.05) and insulin (1.5-fold; P &amp;lt; 0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P &amp;lt; 0.05) insulin sensitivity in the (Pro3)GIP-treated group. Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P &amp;lt; 0.05) and partially corrected the obesity-related islet hypertrophy and \u03b2-cell hyperplasia of ob\/ob mice. These comprehensive beneficial effects of (Pro3)GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes.<\/jats:p>","DOI":"10.2337\/diabetes.54.8.2436","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2436-2446","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":147,"title":["Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes"],"prefix":"10.2337","volume":"54","author":[{"given":"Victor A.","family":"Gault","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Irwin","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Green","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane T.","family":"McCluskey","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Greer","sequence":"additional","affiliation":[{"name":"School of Biology and Biochemistry, Queen\u2019s University of Belfast, Belfast, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford J.","family":"Bailey","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Aston University, Birmingham, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Harriott","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finbarr P.M.","family":"O\u2019Harte","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209030004500_R1","doi-asserted-by":"crossref","unstructured":"Meier JJ, Nauck MA, Schmidt WE, Gallwitz B: Gastric inhibitory polypeptide: the neglected incretin revisited. 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