{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:45:33Z","timestamp":1791877533681,"version":"4.3.4"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,15]]},"abstract":"<jats:p>Glucagon-like peptide-1 (GLP-1) is a potent regulator of glucose-stimulated insulin secretion whose mechanisms of action are only partly understood. In the present paper, we show that at low (3mM) glucose concentrations, GLP-1 increases the free intramitochondrial concentrations of both Ca2+ ([Ca2+]m), and ATP ([ATP]m) in clonal MIN6 \u03b2-cells. Suggesting that cAMP-mediated release of Ca2+ from intracellular stores is responsible for these effects, increases in [ATP]m that were induced by GLP-1 were completely blocked by the Rp isomer of adenosine-3\u2032,5\u2032-cyclic monophosphothioate (Rp-cAMPS), or by chelation of intracellular Ca2+. Furthermore, inhibition of Ins(1,4,5)P3 (IP3) receptors with xestospongin C, or application of ryanodine, partially inhibited GLP-1-induced [ATP]m increases, and the simultaneous blockade of both IP3 and ryanodine receptors (RyR) completely eliminated the rise in [ATP]m. GLP-1 appeared to prompt Ca2+-induced Ca2+ release through IP3 receptors via a protein kinase A (PKA)-mediated phosphorylation event, since ryanodine-insensitive [ATP]m increases were abrogated with the PKA inhibitor, H89. In contrast, the effects of GLP-1 on RyR-mediated [ATP]m increases were apparently mediated by the cAMP-regulated guanine nucleotide exchange factor cAMP-GEFII, since xestospongin C-insensitive [ATP]m increases were blocked by a dominant-negative form of cAMP-GEFII (G114E,G422D). Taken together, these results demonstrate that GLP-1 potentiates glucose-stimulated insulin release in part via the mobilization of intracellular Ca2+, and the stimulation of mitochondrial ATP synthesis.<\/jats:p>","DOI":"10.1042\/bj20021288","type":"journal-article","created":{"date-parts":[[2003,2,19]],"date-time":"2003-02-19T09:39:51Z","timestamp":1045647591000},"page":"287-299","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells"],"prefix":"10.1042","volume":"369","author":[{"given":"Takashi","family":"TSUBOI","sequence":"first","affiliation":[{"name":"Henry Wellcome Laboratories for Integrated Cell Signalling, Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela da","family":"SILVA XAVIER","sequence":"additional","affiliation":[{"name":"Henry Wellcome Laboratories for Integrated Cell Signalling, Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"HOLZ","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016, U.S.A.,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence S.","family":"JOUAVILLE","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ), 185 South Orange Avenue, University Heights, Newark, NJ 07103, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"THOMAS","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ), 185 South Orange Avenue, University Heights, Newark, NJ 07103, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A.","family":"RUTTER","sequence":"additional","affiliation":[{"name":"Henry Wellcome Laboratories for Integrated Cell Signalling, Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/369\/2\/287\/709584\/bj3690287.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/369\/2\/287\/709584\/bj3690287.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T11:58:20Z","timestamp":1637582300000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/369\/2\/287\/39819\/Glucagon-like-peptide-1-mobilizes-intracellular"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,15]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,1,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20021288","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1,15]]}}}