{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T17:14:26Z","timestamp":1676394866458},"reference-count":0,"publisher":"Oxford University Press (OUP)","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:p>OBJECTIVE: Regulation of insulin release by glucose involves dual pathways, including or not inhibition of ATP-sensitive K(+) channels (K(ATP) channels). Whereas the K(ATP) channel-dependent pathway produces pulsatile release of insulin it is not clear whether the independent pathway also generates such kinetics. DESIGN AND METHODS: To clarify this matter, insulin secretion and cytoplasmic Ca(2+) ([Ca(2+)](i)) were studied in perifused pancreatic islets from ob\/ob mice. Insulin release was measured by ELISA technique and [Ca(2+)](i) by dual-wavelength fluorometry. RESULTS: Insulin secretion was pulsatile (0.2--0.3\/min) at 3 mmol\/l glucose when [Ca(2+)](i) was low and stable. Stimulation with 11 mmol\/l of the sugar increased the amplitude of the insulin pulses with maintained frequency and induced oscillations in [Ca(2+)](i). Permanent opening of the K(ATP) channels with diazoxide inhibited glucose-stimulated insulin secretion back to basal levels with maintained pulsatility despite stable and basal [Ca(2+)](i) levels. Increase of the K(+) concentration to 30.9 mmol\/l in the continued presence of diazoxide and 11 mmol\/l glucose restored the secretory rate with maintained pulsatility and caused stable elevation in [Ca(2+)](i). Simultaneous introduction of diazoxide and elevation of K(+) augmented average insulin release almost 30-fold in 3 mmol\/l glucose with maintained pulse frequency. Subsequent elevation of the glucose concentration to 11 and 20 mmol\/l increased the release levels. After prolonged exposure to diazoxide, elevated K(+) and 20 mmol\/l glucose, the pulse frequency decreased significantly. CONCLUSIONS: Not only glucose signaling via the K(ATP) channel-dependent but also that via the independent pathway generates amplitude-modulated pulsatile release of insulin from isolated islets.<\/jats:p>","DOI":"10.1530\/eje.0.1440667","type":"journal-article","created":{"date-parts":[[2005,1,24]],"date-time":"2005-01-24T21:34:41Z","timestamp":1106602481000},"page":"667-675","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":4,"title":["Glucose-regulated pulsatile insulin release from mouse islets via the K(ATP) channel-independent pathway"],"prefix":"10.1093","author":[{"given":"J","family":"Westerlund","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ortsater","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Palm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Sundsten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Bergsten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/144\/6\/667.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/144\/6\/667.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:29:58Z","timestamp":1676392198000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/144\/6\/667\/6750363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1530\/eje.0.1440667","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6,1]]}}}