{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:30:18Z","timestamp":1790479818894,"version":"4.1.0"},"reference-count":28,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":3696,"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":[[2011,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>A progressive decline in insulin responses to glucose was noted in individuals before the onset of type 1 diabetes. We determined whether such abnormalities occurred in prediabetic NOD mice\u2014the prototypic model for human type 1 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Morning blood glucose was measured every other day in a cohort of NOD females. Glucose tolerance and insulin secretion were measured longitudinally by intraperitoneal glucose tolerance tests in NOD\/ShiLtJ and BALB\/cJ mice 6 to 14 weeks of age. Arginine-stimulated insulin secretion and insulin sensitivity were assessed during intraperitoneal arginine or intraperitoneal insulin tolerance tests.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>During prediabetes, NOD females displayed a progressive increase in glucose levels followed by an acute onset of hyperglycemia. First-phase insulin responses (FPIRs) during the intraperitoneal glucose tolerance test (IPGTT) declined before loss of glucose tolerance in NOD. The failure of FPIR could be detected, with a decline in peak insulin secretion during IPGTT. Arginine-stimulated insulin secretion remained unchanged during the study period. The decline in insulin secretion in NOD mice could not be explained by changes in insulin sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>There was an impressive decline in FPIR before changes in glucose tolerance, suggesting that impairment of FPIR is an early in vivo marker of progressive \u03b2-cell failure in NOD mice and human type 1 diabetes. We portend that these phenotypes in NOD mice follow a similar pattern to those seen in humans with type 1 diabetes and validate, in a novel way, the importance of this animal model for studies of this disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db11-0373","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T08:55:51Z","timestamp":1307696151000},"page":"2086-2091","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":70,"title":["Progressive Erosion of \u03b2-Cell Function Precedes the Onset of Hyperglycemia in the NOD Mouse Model of Type 1 Diabetes"],"prefix":"10.2337","volume":"60","author":[{"given":"Diego","family":"Ize-Ludlow","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology, Diabetes and Metabolism, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaima L.","family":"Lightfoot","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Wasserfall","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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