{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:55:14Z","timestamp":1768006514845,"version":"3.49.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":2752,"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":[[2014,3,1]]},"abstract":"<jats:p>Understanding the incretin pathway has led to significant advancements in the treatment of type 2 diabetes (T2D). Still, the exact mechanisms are not fully understood. In a randomized, placebo-controlled, four-period, crossover study in 24 patients with T2D, dipeptidyl peptidase-4 (DPP-4) inhibition and its glucose-lowering actions were tested after an oral glucose tolerance test (OGTT). The contribution of GLP-1 was examined by infusion of the GLP-1 receptor (GLP-1r) antagonist exendin-9. DPP-4 inhibition reduced glycemia and enhanced insulin levels and the incretin effect (IE). Glucagon was suppressed, and gastric emptying (GE) was decelerated. Exendin-9 increased glucose levels and glucagon secretion, attenuated insulinemia and the IE, and accelerated GE. With the GLP-1r antagonist, the glucose-lowering effects of DPP-4 inhibition were reduced by \u223c50%. However, a significant effect on insulin secretion remained during GLP-1r blockade, whereas the inhibitory effects of DPP-4 inhibition on glucagon and GE were abolished. Thus, in this cohort of T2D patients with a substantial IE, GLP-1 contributed \u223c50% to the insulin excursion after an OGTT with and without DPP-4 inhibition. Thus, a significant DPP-4\u2013sensitive glucose-lowering mechanism contributes to glycemic control in T2D patients that may be not mediated by circulating GLP-1.<\/jats:p>","DOI":"10.2337\/db13-1455","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T05:13:59Z","timestamp":1386047639000},"page":"1079-1092","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":85,"title":["Defining the Role of GLP-1 in the Enteroinsulinar Axis in Type 2 Diabetes Using DPP-4 Inhibition and GLP-1 Receptor Blockade"],"prefix":"10.2337","volume":"63","author":[{"given":"Benedikt A.","family":"Aulinger","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Clinical Research Unit, Clinical Center of the Ludwig-Maximilians University, Campus Grosshadern, Munich, 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