{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:06:11Z","timestamp":1791133571437,"version":"4.1.0"},"reference-count":0,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:p>Chronic hyperglycemia desensitizes beta-cells to glucose. To further define the mechanisms behind desensitization and the role of overstimulation, we tested human pancreatic islets for the effects of long-term elevated glucose levels on cytoplasmic free Ca2+ concentration ([Ca2+]i) and its relationship to overstimulation. Islets were cultured for 48 h with 5.5 or 27 mmol\/l glucose. Culture with 27 mmol\/l glucose obliterated postculture insulin responses to 27 mmol\/l glucose. This desensitization was specific for glucose versus arginine. Desensitization was accompanied by three major [Ca2+]i abnormalities: 1) elevated basal [Ca2+]i, 2) loss of a glucose-induced rise in [Ca2+]i, and 3) perturbations of oscillatory activity with a decrease in glucose-induced slow oscillations (0.2-0.5 min(-1)). Coculture with 0.3 mmol\/l diazoxide was performed to probe the role of overstimulation. Neither glucose nor diazoxide affected islet glucose utilization or oxidation. Coculture with diazoxide and 27 mmol\/l glucose significantly (P &amp;lt; 0.05) restored postculture insulin responses to glucose and lowered basal [Ca2+]i and normalized glucose-induced oscillatory activity. However, diazoxide completely failed to revive an increase in [Ca2+]i during postculture glucose stimulation. In conclusion, desensitization of glucose-induced insulin secretion in human pancreatic islets is induced in parallel with major glucose-specific [Ca2+]i abnormalities. Overstimulation is an important but not exclusive factor behind [Ca2+]i abnormalities.<\/jats:p>","DOI":"10.2337\/diabetes.49.11.1840","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1840-1848","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":58,"title":["Glucose-induced [Ca2+]i abnormalities in human pancreatic islets: important role of overstimulation."],"prefix":"10.2337","volume":"49","author":[{"given":"A","family":"Bj\u00f6rklund","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. anneli.bjorklund@molmed.ki.se"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Lansner","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. anneli.bjorklund@molmed.ki.se"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V E","family":"Grill","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. anneli.bjorklund@molmed.ki.se"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/49\/11\/1840\/364929\/11078450.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/49\/11\/1840\/364929\/11078450.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:49:38Z","timestamp":1667407778000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/49\/11\/1840\/10480\/Glucose-induced-Ca2-i-abnormalities-in-human"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11,1]]},"references-count":0,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2000,11,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.49.11.1840","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11,1]]}}}