{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:43:34Z","timestamp":1791359014938,"version":"4.3.1"},"reference-count":0,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,8,1]]},"abstract":"<jats:p>The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1 act on the pancreas to potentiate glucose-induced insulin secretion (enteroinsular axis). These hormones (incretins) are rapidly hydrolyzed by the circulating enzyme dipeptidyl peptidase IV (DP IV) into biologically inactive NHg-terminally truncated fragments. This study describes the effect of inhibiting endogenous DP IV with a specific DP IV inhibitor, isoleucine thiazolidide (Ile-thiazolidide), on glucose tolerance and insulin secretion in the obese Zucker rat. In initial studies, the specificity of Ile-thiazolidide as an inhibitor of incretin degradation was determined using matrix-assisted laser desorption7sol;ionization-time of flight mass spectrometry. These results showed that inhibiting DP IV activity with Ile-thiazolidide blocked the formation of NH2-terminally truncated GIP and GLP-1. Oral administration of Ile-thiazolidide resulted in rapid inhibition of circulating DP IV levels by 65% in obese and lean Zucker rats. Suppression of DP IV levels enhanced insulin secretion in both phenotypes with the most dramatic effect occurring in obese animals (150% increase in integrated insulin response vs. 27% increase in lean animals). Ile-thiazolidide treatment improved glucose tolerance in both phenotypes and restored glucose tolerance to near-normal levels in obese animals. This was attributed to the glucose-lowering actions of increasing the circulating half-lives of the endogenously released incretins GIP and, particularly, GLP-1. This study suggests that drug manipulation of plasma incretin activity by inhibiting the enzyme DP IV is a valid therapeutic approach for lowering glucose levels in NIDDM and other disorders involving glucose intolerance.<\/jats:p>","DOI":"10.2337\/diab.47.8.1253","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:42:54Z","timestamp":1379612574000},"page":"1253-1258","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":231,"title":["Improved Glucose Tolerance in Zucker Fatty Rats by Oral Administration of the Dipeptidyl Peptidase IV Inhibitor Isoleucine Thiazolidide"],"prefix":"10.2337","volume":"47","author":[{"given":"Raymond A","family":"Pederson","sequence":"first","affiliation":[{"name":"Department of Physiology, University of British Columbia\u2008Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A","family":"White","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of British Columbia\u2008Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Schlenzig","sequence":"additional","affiliation":[{"name":"Department of Drug Biochemistry, Hans Knoell Institute for Natural Product Research\u2008Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P","family":"Pauly","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of British Columbia\u2008Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H S","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of British Columbia\u2008Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Ulrich","family":"Demuth","sequence":"additional","affiliation":[{"name":"Department of Drug Biochemistry, Hans Knoell Institute for Natural Product Research\u2008Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/47\/8\/1253\/364118\/47-8-1253.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/47\/8\/1253\/364118\/47-8-1253.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:35:01Z","timestamp":1667406901000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/47\/8\/1253\/11985\/Improved-Glucose-Tolerance-in-Zucker-Fatty-Rats-by"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,8,1]]},"references-count":0,"aliases":["10.2337\/diabetes.47.8.1253"],"journal-issue":{"issue":"8","published-print":{"date-parts":[[1998,8,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.47.8.1253","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,8,1]]}}}