{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:10:25Z","timestamp":1779343825605,"version":"3.51.4"},"reference-count":0,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,7,1]]},"abstract":"<jats:p>IA-2, a member of the protein tyrosine phosphatase family, represents a major target autoantigen in type 1 diabetes. To study the regulation of IA-2 gene expression, we used INS-1 insulinoma cells to analyze beta-cell signal transduction pathways as well as the effect of metabolic and hormonal factors involved in the regulation of the insulin secretory pathway. Quantitative competitive reverse transcriptase-polymerase chain reaction revealed that an increase of cellular cAMP mediated by forskolin (10 micromol\/l, 24 h) or 3-isobutyl-1-methylxanthine (100 micromol\/l, 24 h) induced maximal stimulation of IA-2 mRNA levels (451 +\/- 85 and 338 +\/- 86% compared with basal conditions; P &amp;lt; 0.001). In contrast, activation of protein kinase C (PKC) by short-term treatment with phorbol 12-myristate 13-acetate (PMA) (1 micromol\/l, 6 h) did not alter IA-2 expression, whereas depletion of PKC by prolonged culturing (24 h) exerted a significant inhibition (57 +\/- 24%; P &amp;lt; 0.05). cAMP-dependent upregulation was confirmed by the findings that glucagon (10 micromol\/l, 24-48 h) increased levels of IA-2 mRNA (190 +\/- 35%; P &amp;lt; 0.05), whereas short-term incubation with high glucose concentration showed no effect. However, prolonged incubation in high glucose (21 mmol\/l) induced a time- and dose-dependent increase of IA-2 mRNA expression, reaching maximal values after 144 h (285 +\/- 68%; P &amp;lt; 0.05). These studies demonstrate that stimuli of insulin secretion that operate by activation of adenylate cyclase generating cAMP significantly increase IA-2 gene expression. In contrast, activation of PKC by high glucose concentration or PMA exerted no effect, suggesting that IA-2 gene expression is not simply coupled to insulin secretion, but may be involved in the fine regulation of beta-cell function. These findings may be important to clarify the function of IA-2 in beta-cells and elucidate mechanisms involved in the induction of autoimmunity to IA-2.<\/jats:p>","DOI":"10.2337\/diabetes.49.7.1137","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1137-1141","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":16,"title":["Regulation of the diabetes-associated autoantigen IA-2 in INS-1 pancreatic beta-cells."],"prefix":"10.2337","volume":"49","author":[{"given":"J","family":"Seissler","sequence":"first","affiliation":[{"name":"Diabetes Research Institute, University of D\u00fcsseldorf, Germany. sei@dfi.uni-duesseldorf.de"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T B","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of D\u00fcsseldorf, Germany. sei@dfi.uni-duesseldorf.de"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Aust","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of D\u00fcsseldorf, Germany. sei@dfi.uni-duesseldorf.de"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Steinbrenner","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of D\u00fcsseldorf, Germany. sei@dfi.uni-duesseldorf.de"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W A","family":"Scherbaum","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of D\u00fcsseldorf, Germany. sei@dfi.uni-duesseldorf.de"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/49\/7\/1137\/338429\/10909970.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/49\/7\/1137\/338429\/10909970.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:07:33Z","timestamp":1667405253000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/49\/7\/1137\/12196\/Regulation-of-the-diabetes-associated-autoantigen"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,7,1]]},"references-count":0,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2000,7,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.49.7.1137","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,7,1]]}}}