{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:12:44Z","timestamp":1787508764616,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3469,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,8]]},"abstract":"\n \n \n \n To determine how pretreatment with sulphonylureas alters the \u03b2 cell function, mouse islets were cultured (18\u201320\u2003h) without (controls) or with (test) 0.01\u2003\u03bc\n M<\/jats:sc>\n glibenclamide. Acute responses to glucose were then determined in the absence of glibenclamide.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Test islets were insensitive to drugs (sulphonylureas and diazoxide) acting on K\n +<\/jats:sup>\n \u2010ATP channels, and their [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n was already elevated in the absence of stimulation.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Insulin secretion was increased in the absence of glucose, and mainly stimulated between 0\u201310 instead of 7\u201320\u2003m\n M<\/jats:sc>\n glucose in controls. The maximum response was halved, but this difference disappeared after correction for the 45% decrease in the islet insulin content.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The first phase of glucose\u2010induced insulin secretion was abrogated because of a paradoxical decrease of the high basal [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n in \u03b2 cells. The second phase was preserved but occurred with little rise of [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n . These abnormalities did not result from alterations of glucose metabolism (NADPH fluorescence).\n <\/jats:p>\n <\/jats:list-item>\n \n \n In islets cultured with 50\u2003\u03bc\n M<\/jats:sc>\n tolbutamide, glucose induced biphasic increases in [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n and insulin secretion. The decrease in the secretory response was matched by the decrease in insulin content (45%) except at maximal glucose concentrations. Islets pretreated with tolbutamide, however, behaved like those cultured with glibenclamide if tolbutamide was also present during the acute functional tests.\n <\/jats:p>\n <\/jats:list-item>\n \n \n In conclusion, treatment with a low glibenclamide concentration causes long\u2010lasting blockade of K\n +<\/jats:sup>\n \u2010ATP channels and rise of [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n in \u03b2 cells. Glucose\u2010induced insulin secretion occurs at lower concentrations, is delayed and is largely mediated by a modulation of Ca\n 2+<\/jats:sup>\n action on exocytosis. It is suggested that glucose regulation of insulin secretion mainly depends on a K\n +<\/jats:sup>\n \u2010ATP channel\u2010independent pathway during\n in vivo<\/jats:italic>\n sulphonylurea treatment.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n \n British Journal of Pharmacology<\/jats:italic>\n (1999)\n 127<\/jats:bold>\n , 1883\u20131891; doi:\n 10.1038\/sj.bjp.0702731<\/jats:ext-link>\n <\/jats:p>","DOI":"10.1038\/sj.bjp.0702731","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T15:24:28Z","timestamp":1106925868000},"page":"1883-1891","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Alterations of insulin secretion from mouse islets treated with sulphonylureas: perturbations of Ca\n 2+<\/sup>\n regulation prevail over changes in insulin content"],"prefix":"10.1111","volume":"127","author":[{"given":"Marcello","family":"Anello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Gilon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Claude","family":"Henquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.1.227"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01225-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90330-L"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02056108"},{"key":"e_1_2_7_6_1","first-page":"229","article-title":"Pharmacological interaction between tolbutamide and acetylsalicylic acid: study on insulin secretion in man","volume":"28","author":"CATTANEO A.G.","year":"1990","journal-title":"Int. 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