{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:43:59Z","timestamp":1791297839543,"version":"4.1.0"},"reference-count":42,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":4204,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>The insulinotropic action of the incretin glucose-dependent insulinotropic polypeptide (GIP) is impaired in type 2 diabetes, while the effect of glucagon-like peptide-1 (GLP-1) is preserved. To evaluate the role of impaired GIP function in glucose homeostasis and development of the endocrine pancreas in a large animal model, we generated transgenic pigs expressing a dominant-negative GIP receptor (GIPRdn) in pancreatic islets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>GIPRdn transgenic pigs were generated using lentiviral transgenesis. Metabolic tests and quantitative stereological analyses of the different endocrine islet cell populations were performed, and \u03b2-cell proliferation and apoptosis were quantified to characterize this novel animal model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Eleven-week-old GIPRdn transgenic pigs exhibited significantly reduced oral glucose tolerance due to delayed insulin secretion, whereas intravenous glucose tolerance and pancreatic \u03b2-cell mass were not different from controls. The insulinotropic effect of GIP was significantly reduced, whereas insulin secretion in response to the GLP-1 receptor agonist exendin-4 was enhanced in GIPRdn transgenic versus control pigs. With increasing age, glucose control deteriorated in GIPRdn transgenic pigs, as shown by reduced oral and intravenous glucose tolerance due to impaired insulin secretion. Importantly, \u03b2-cell proliferation was reduced by 60% in 11-week-old GIPRdn transgenic pigs, leading to a reduction of \u03b2-cell mass by 35% and 58% in 5-month-old and 1- to 1.4-year-old transgenic pigs compared with age-matched controls, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The first large animal model with impaired incretin function demonstrates an essential role of GIP for insulin secretion, proliferation of \u03b2-cells, and physiological expansion of \u03b2-cell mass.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db09-0519","type":"journal-article","created":{"date-parts":[[2010,2,26]],"date-time":"2010-02-26T03:41:37Z","timestamp":1267155697000},"page":"1228-1238","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":154,"title":["Glucose Intolerance and Reduced Proliferation of Pancreatic \u03b2-Cells in Transgenic Pigs With Impaired Glucose-Dependent Insulinotropic Polypeptide Function"],"prefix":"10.2337","volume":"59","author":[{"given":"Simone","family":"Renner","sequence":"first","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis, Gene Center, Ludwig Maximilians University (LMU) Munich, Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Fehlings","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis, Gene Center, Ludwig Maximilians University (LMU) Munich, Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Herbach","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Faculty of Veterinary Medicine, LMU Munich, Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar C.","family":"von Waldthausen","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis, Gene Center, Ludwig Maximilians University (LMU) Munich, Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kessler","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology and Laboratory for Functional Genome Analysis, Gene Center, Ludwig Maximilians University (LMU) Munich, Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Ulrichs","sequence":"additional","affiliation":[{"name":"Department of Experimental Transplantation Immunology, Surgical Clinic I, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Chodnevskaja","sequence":"additional","affiliation":[{"name":"Department of Experimental Transplantation Immunology, Surgical Clinic I, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliy","family":"Moskalenko","sequence":"additional","affiliation":[{"name":"Department of Experimental Transplantation Immunology, Surgical Clinic I, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Amselgruber","sequence":"additional","affiliation":[{"name":"Institute of 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