{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:49:55Z","timestamp":1753886995764,"version":"3.41.2"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,3,6]]},"abstract":"\n Background<\/jats:title>\n \n Diminished growth hormone (\n GH<\/jats:styled-content>\n ) is associated with impaired endothelial function and fibrinolysis.\n GH<\/jats:styled-content>\n \u2010releasing hormone is the primary stimulus for\n GH<\/jats:styled-content>\n secretion and a substrate of dipeptidyl peptidase\u20104. We tested the hypothesis that dipeptidyl peptidase\u20104 inhibition with sitagliptin increases stimulated\n GH<\/jats:styled-content>\n secretion, vasodilation, and tissue plasminogen activator (\n tPA<\/jats:styled-content>\n ) activity.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Healthy adults participated in a 2\u2010part double\u2010blind, randomized, placebo\u2010controlled, crossover study. First, 39 patients (29 women) received sitagliptin or placebo on each of 2\u00a0days separated by a washout. One hour after study drug, blood was sampled and then arginine (30\u00a0g IV) was given to stimulate\n GH<\/jats:styled-content>\n . Vasodilation was assessed by plethysmography and blood sampled for 150\u00a0minutes. Following a washout, 19 of the original 29 women received sitagliptin alone versus sitagliptin plus antagonist to delineate\n GH<\/jats:styled-content>\n receptor (\n GHR<\/jats:styled-content>\n )\u2013 (n=5), nitric oxide\u2013 (n=7), or glucagon\u2010like peptide\u20101 receptor\u2013 (n=7) dependent effects. Sitagliptin enhanced stimulated\n GH<\/jats:styled-content>\n secretion (\n P<\/jats:italic>\n <0.01 versus placebo, for 30\u00a0minutes) and free insulin\u2013like growth factor\u20101 (\n P<\/jats:italic>\n <0.001 versus placebo, after adjustment for baseline) in women. Vasodilation and\n tPA<\/jats:styled-content>\n increased in all patients, but sitagliptin enhanced vasodilation (\n P<\/jats:italic>\n =0.01 versus placebo) and increased\n tPA<\/jats:styled-content>\n (\n P<\/jats:italic>\n <0.001) in women only.\n GHR<\/jats:styled-content>\n blockade decreased free insulin\u2013like growth factor\u20101 (\n P<\/jats:italic>\n =0.04 versus sitagliptin alone) and increased stimulated\n GH<\/jats:styled-content>\n (\n P<\/jats:italic>\n <0.01), but decreased vascular resistance (\n P<\/jats:italic>\n =0.01) such that nadir vascular resistance correlated inversely with\n GH<\/jats:styled-content>\n (\n r<\/jats:italic>\n s<\/jats:sub>\n =\u22120.90,\n P<\/jats:italic>\n <0.001).\n GHR<\/jats:styled-content>\n blockade suppressed\n tPA<\/jats:styled-content>\n . Neither nitric oxide nor glucagon\u2010like peptide\u20101 receptor blockade affected vasodilation or\n tPA<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Sitagliptin enhances stimulated\n GH<\/jats:styled-content>\n , vasodilation, and fibrinolysis in women. During sitagliptin, increases in free insulin\u2013like growth factor\u20101 and\n tPA<\/jats:styled-content>\n occur via the\n GHR<\/jats:styled-content>\n , whereas vasodilation correlates with\n GH<\/jats:styled-content>\n but occurs through a\n GHR<\/jats:styled-content>\n \u2010independent mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier:\n NCT<\/jats:styled-content>\n 01701973.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.008000","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T02:16:18Z","timestamp":1519611378000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Dipeptidyl Peptidase\u20104 Inhibition Potentiates Stimulated Growth Hormone Secretion and Vasodilation in Women"],"prefix":"10.1161","volume":"7","author":[{"given":"Jessica R.","family":"Wilson","sequence":"first","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Nian","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bidlingmaier","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica K.","family":"Devin","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1990.tb11600.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1470523"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2021"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030144"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0609"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2013.08.005"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2007.11.001"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-008-0092-8"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1995.tb02691.x"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/434562"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000027563.44593.CC"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-139-8-200310210-00007"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3968"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0169"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112679"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(65)90399-5"},{"key":"e_1_3_5_18_2","first-page":"1072","article-title":"Insights from growth hormone receptor blockade","volume":"5","author":"Muller AF","year":"2004","unstructured":"Muller AF, van der Lely AJ. 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