{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T02:07:11Z","timestamp":1772849231713,"version":"3.50.1"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:p>Islet antigen-2 (IA-2 or ICA 512) and IA-2\u03b2 (or phogrin) are major autoantigens in type 1 diabetes. They are located in dense core secretory vesicles including insulin granules, but their role in \u03b2-cell function is unclear. Targeted disruption of either IA-2 or IA-2\u03b2, or both, impaired glucose tolerance, an effect attributed to diminution of insulin secretion. In this study, we therefore characterized the dynamic changes in cytosolic Ca<jats:sup>2+<\/jats:sup>([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>) and insulin secretion in islets from IA-2\/IA-2\u03b2 double knockout (KO) mice. High glucose (15\u200amM) induced biphasic insulin secretion in IA-2\/IA-2\u03b2 KO islets, with a similar first phase and smaller second phase compared with controls. Since the insulin content of IA-2\/IA-2\u03b2 KO islets was \u223c45% less than that of controls, fractional insulin secretion (relative to content) was thus increased during first phase and unaffected during second phase. This peculiar response occurred in spite of a slightly smaller rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>, could not be attributed to an alteration of glucose metabolism (NADPH fluorescence) and also was observed with tolbutamide. The dual control of insulin secretion via the K<jats:sub>ATP<\/jats:sub> channel-dependent triggering pathway and K<jats:sub>ATP<\/jats:sub> channel-independent amplifying pathway was unaltered in IA-2\/IA-2\u03b2 KO islets, and so were the potentiations by acetylcholine or cAMP (forskolin). Intriguingly, amino acids, in particular the cationic arginine and lysine, induced larger fractional insulin secretion in IA-2\/IA-2\u03b2 KO than control islets. In conclusion, IA-2 and IA-2\u03b2 are dispensable for exocytosis of insulin granules, but are probably more important for cargo loading and\/or stability of dense core vesicles.<\/jats:p>","DOI":"10.1677\/joe-07-0496","type":"journal-article","created":{"date-parts":[[2008,2,29]],"date-time":"2008-02-29T18:52:07Z","timestamp":1204311127000},"page":"573-581","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":36,"title":["Insulin secretion in islets from mice with a double knockout for the dense core vesicle proteins islet antigen-2 (IA-2) and IA-2\u03b2"],"prefix":"10.1530","volume":"196","author":[{"given":"Jean-Claude","family":"Henquin","sequence":"first","affiliation":[]},{"given":"Myriam","family":"Nenquin","sequence":"additional","affiliation":[]},{"given":"Andras","family":"Szollosi","sequence":"additional","affiliation":[]},{"given":"Atsutaka","family":"Kubosaki","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and MetabolismFaculty of Medicine, University of Louvain, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium1Experimental Medicine SectionOral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda 20891, MD, USA"}]},{"given":"Abner","family":"Louis Notkins","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and MetabolismFaculty of Medicine, University of Louvain, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium1Experimental Medicine SectionOral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda 20891, MD, USA"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/196\/3\/573.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/196\/3\/573.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T22:14:43Z","timestamp":1609798483000},"score":1,"resource":{"primary":{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/196\/3\/573.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,10]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1677\/joe-07-0496","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,10]]}}}