{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:21:02Z","timestamp":1791174062396,"version":"4.1.0"},"reference-count":0,"publisher":"American Diabetes Association","issue":"10","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,10,1]]},"abstract":"<jats:p>1-Cells from rodents and humans express different receptors recognizing hormones of the secretin-glucagon family, which--when activated--synergize with glucose in the control of insulin release. We have recently reported that isolated islets from mice homozygous for a GLP-1 receptor null mutation (GLP-1R(-\/-)) exhibit a well-preserved insulin-secretory response to glucose. This observation can be interpreted in two different ways: 1) the presence of GLP-1R is not essential for the secretory response of isolated islets to glucose alone; 2) beta-cells in GLP-1R(-\/-) pancreases underwent compensatory changes in response to the null mutation. To explore these possibilities, we studied islets from control GLP-IR(+\/+) mice in the absence or presence of 1 pmol\/l exendin (9-39)amide, a specific and potent GLP-1R antagonist. Exendin (9-39)amide (15-min exposure) reduced glucose-induced insulin secretion from both perifused and statically incubated GLP-1R(+\/+) islets by 50% (P &amp;lt; 0.05), and reduced islet cAMP production in parallel (P &amp;lt; 0.001). Furthermore, GLP-1R(-\/-) islets exhibited: 1) reduced cAMP accumulation in the presence of 20 mmol\/l glucose (knockout islets versus control islets, 12 +\/- 1 vs. 27 +\/- 3 fmol x islet(-1) x 15 min(-1); P &amp;lt; 0.001) and exaggerated acceleration of cAMP production by 10 nmol\/l glucose-dependent insulinotropic peptide (GIP) (increase over 20 mmol\/l glucose by GIP in knockout islets versus control islets: 66 +\/- 5 vs. 14 +\/- 3 fmol x islet(-1) x 15 min(-1); P &amp;lt; 0.001); 2) increased mean cytosolic [Ca2+] ([Ca2+]c) at 7, 10, and 15 mmol\/l glucose in knockout islets versus control islets; and 3) signs of asynchrony of [Ca2+]c oscillations between different islet subregions. In conclusion, disruption of GLP-1R signaling is associated with reduced basal but enhanced GIP-stimulated cAMP production and abnormalities in basal and glucose-stimulated [Ca2+]c. These abnormalities suggest that GLP-1R signaling is an essential upstream component of multiple beta-cell signaling pathways.<\/jats:p>","DOI":"10.2337\/diabetes.48.10.1979","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1979-1986","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":54,"title":["Altered cAMP and Ca2+ signaling in mouse pancreatic islets with glucagon-like peptide-1 receptor null phenotype."],"prefix":"10.2337","volume":"48","author":[{"given":"D","family":"Flamez","sequence":"first","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Gilon","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Moens","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Van Breusegem","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Delmeire","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L A","family":"Scrocchi","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Henquin","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Drucker","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Schuit","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/48\/10\/1979\/363594\/10512362.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/48\/10\/1979\/363594\/10512362.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:46:10Z","timestamp":1667407570000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/48\/10\/1979\/11406\/Altered-cAMP-and-Ca2-signaling-in-mouse-pancreatic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,10,1]]},"references-count":0,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1999,10,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.48.10.1979","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,10,1]]}}}