{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:36:10Z","timestamp":1789378570871,"version":"build-2803163510"},"reference-count":0,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:p>Leptin and glucagon-like peptide 1 (GLP-1) exhibit opposing actions in the endocrine pancreas. GLP-1 stimulates insulin biosynthesis, secretion, and islet growth, whereas leptin inhibits glucose-dependent insulin secretion and insulin gene transcription. In contrast, GLP-1 and leptin actions overlap in the central nervous system, where leptin has been shown to activate GLP-1 circuits that inhibit food intake. To determine the physiological importance of GLP-1 receptor (GLP-1R)-leptin interactions, we studied islet function and feeding behavior in ob\/ob:GLP-1R(-\/-) mice. Although GLP-1R actions are thought to be essential for glucose-dependent insulin secretion, the levels of fasting glucose, glycemic excursion after glucose loading, glucose-stimulated insulin, and pancreatic insulin RNA content were similar in ob\/ob:GLP-1R(+\/+) versus ob\/ob:GLP-1R(-\/-) mice. Despite evidence linking GLP-1R signaling to the regulation of islet neogenesis and proliferation, ob\/ob:GLP-1R(-\/-) mice exhibited significantly increased islet numbers and area and an increase in the number of large islets compared with GLP-1R(+\/+) or (-\/-) mice (P &amp;lt; -0.01 to 0.05). Similarly, growth rates and both shortand long-term control of food intake were comparable in ob\/ob:GLP-1R(+\/+) versus ob\/ob:GLP-1R4(-\/-) mice. Furthermore, leptin produced a similar inhibition of food intake in GLP-1R(-\/-), ob\/ob:GLP-1R(+\/+), and ob\/ob:GLP1R4(-\/-) mice. These findings illustrate that although leptin and GLP-1 actions overlap in the brain and endocrine pancreas, disruption of GLP-1 signaling does not modify the response to leptin or the phenotype of leptin deficiency in the ob\/ob mouse, as assessed by long-term control of body weight or the adaptive beta-cell response to insulin resistance in vivo.<\/jats:p>","DOI":"10.2337\/diabetes.49.9.1552","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1552-1560","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":51,"title":["Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action."],"prefix":"10.2337","volume":"49","author":[{"given":"L A","family":"Scrocchi","sequence":"first","affiliation":[{"name":"Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M E","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Drucker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/49\/9\/1552\/365378\/10969840.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/49\/9\/1552\/365378\/10969840.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:08:04Z","timestamp":1667405284000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/49\/9\/1552\/10783\/Elimination-of-glucagon-like-peptide-1R-signaling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9,1]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2000,9,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.49.9.1552","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,9,1]]}}}