{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:36:45Z","timestamp":1789763805549,"version":"4.0.1"},"reference-count":42,"publisher":"American Diabetes Association","issue":"6","license":[{"start":{"date-parts":[[2017,5,22]],"date-time":"2017-05-22T00:00:00Z","timestamp":1495411200000},"content-version":"vor","delay-in-days":81,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100007476","name":"Canadian Diabetes Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007476","name":"Canadian Diabetes Association","doi-asserted-by":"publisher","award":["OG-3-11-3270-DD"],"award-info":[{"award-number":["OG-3-11-3270-DD"]}],"id":[{"id":"10.13039\/100007476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000035","name":"Institute of Nutrition, Metabolism and Diabetes","doi-asserted-by":"publisher","award":["123391"],"award-info":[{"award-number":["123391"]}],"id":[{"id":"10.13039\/501100000035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007476","name":"Canadian Diabetes Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:p>GPR119 was originally identified as an orphan \u03b2-cell receptor; however, subsequent studies demonstrated that GPR119 also regulates \u03b2-cell function indirectly through incretin hormone secretion. We assessed the importance of GPR119 for \u03b2-cell function in Gpr119\u2212\/\u2212 mice and in newly generated Gpr119\u03b2cell\u2212\/\u2212 mice. Gpr119\u2212\/\u2212 mice displayed normal body weight and glucose tolerance on a regular chow (RC) diet. After high-fat feeding, Gpr119\u2212\/\u2212 mice exhibited reduced fat mass, decreased levels of circulating adipokines, improved insulin sensitivity, and better glucose tolerance. Unexpectedly, oral and intraperitoneal glucose tolerance and the insulin response to glycemic challenge were not perturbed in Gpr119\u03b2cell\u2212\/\u2212 mice on RC and high-fat diets. Moreover, islets from Gpr119\u2212\/\u2212 and Gpr119\u03b2cell\u2212\/\u2212 mice exhibited normal insulin responses to glucose and \u03b2-cell secretagogues. Furthermore, the selective GPR119 agonist AR231453 failed to directly enhance insulin secretion from perifused islets. In contrast, AR231453 increased plasma glucagon-like peptide 1 (GLP-1) and insulin levels and improved glucose tolerance in wild-type and Gpr119\u03b2cell\u2212\/\u2212 mice. These findings demonstrate that \u03b2-cell GPR119 expression is dispensable for the physiological control of insulin secretion and the pharmacological response to GPR119 agonism, findings that may inform the lack of robust efficacy in clinical programs assessing GPR119 agonists for the therapy of type 2 diabetes.<\/jats:p>","DOI":"10.2337\/db17-0017","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T01:40:30Z","timestamp":1488505230000},"page":"1626-1635","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":28,"title":["\u03b2-Cell Inactivation of <i>Gpr119<\/i> Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation"],"prefix":"10.2337","volume":"66","author":[{"given":"Brandon L.","family":"Panaro","sequence":"first","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, 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