{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:26:17Z","timestamp":1761128777077},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Nateglinide restores early-phase insulin secretion to feeding and reduces postprandial hyperglycaemia in type 2 diabetes. This study evaluated the effects of nateglinide on dipeptidyl peptidase-IV (DPP-IV) activity and glucose-dependent insulinotropic polypeptide (GIP) degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Research design and methods<\/jats:title><jats:p>Blood samples were collected from type 2 diabetic subjects (<jats:italic>n<\/jats:italic>=10, fasting glucose 9.36\u00b11.2\u200ammol\/l) following administration of oral nateglinide (120\u200amg) 10\u200amin prior to a 75\u200ag oral glucose load in a randomised crossover design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma glucose reached 18.2\u00b11.7 and 16.7\u00b11.7\u200ammol\/l at 90\u200amin in control and placebo groups (<jats:italic>P<\/jats:italic>&lt;0.001). These effects were accompanied by prompt 32% inhibition of DPP-IV activity after 10\u200amin (19.9\u00b11.6\u200anmol\/ml per min, <jats:italic>P<\/jats:italic>&lt;0.05), reaching a minimum of 1.9\u00b10.1\u200anmol\/ml per min at 120\u200amin (<jats:italic>P<\/jats:italic>&lt;0.001) after nateglinide. Insulin and C-peptide levels increased significantly compared with placebo, to peak after 90\u200amin at 637.6\u00b1163.9\u200apmol\/l (<jats:italic>P<\/jats:italic>&lt;0.05) and 11.8\u00b11.4\u200amg\/l (<jats:italic>P<\/jats:italic>&lt;0.01) respectively. DPP-IV-mediated degradation of GIP was significantly less in patients receiving nateglinide compared with placebo. Inhibition of DPP-IV activity corresponded with a time- and concentration-dependent inhibitory effect of nateglinide on DPP-IV-mediated truncation of GIP(1\u201342) to GIP(3\u201342) <jats:italic>in vitro<\/jats:italic>. Comparison of <jats:italic>in vitro<\/jats:italic> inhibition of DPP-IV by nateglinide and vildagliptin revealed IC<jats:sub>50<\/jats:sub> values of 17.1 and 2.1\u200a\u03bcM respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although considerably less potent than specified DPP-IV inhibitors, the possibility that some of the beneficial actions of nateglinide are indirectly mediated through DPP-IV inhibition and increased bioavailability of GIP and other incretins merits consideration.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-09-0547","type":"journal-article","created":{"date-parts":[[2009,9,16]],"date-time":"2009-09-16T03:09:20Z","timestamp":1253070560000},"page":"877-885","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":15,"title":["Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation"],"prefix":"10.1093","volume":"161","author":[{"given":"Aine M","family":"McKillop","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola A","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R","family":"Lindsay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian D","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finbarr P M","family":"O'Harte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick M","family":"Bell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R","family":"Flatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/161\/6\/877.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/161\/6\/877.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:23:49Z","timestamp":1676391829000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/161\/6\/877\/6676398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-09-0547","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12]]}}}