{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T10:15:31Z","timestamp":1753438531674},"reference-count":28,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,11,5]],"date-time":"2012-11-05T00:00:00Z","timestamp":1352073600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>ZAC (Zinc finger protein that regulates apoptosis and cell\u2010cycle arrest) is a candidate gene for transient neonatal diabetes mellitus (TNDM). This condition involves severe insulin deficiency at birth that reverses over weeks or months but may relapse with diabetes recurring in later life. ZAC overexpression in transgenic mice has previously been shown to result in complex changes in both beta\u2010cell mass and possibly function. The present study therefore aimed to examine the role of ZAC in beta\u2010cell function <jats:italic>in vitro<\/jats:italic>, independent of the confounder of a reduced beta\u2010cell mass at birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Overexpression of ZAC was achieved through the tetracycline\u2010regulatable system in the beta\u2010cell line, INS\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that ZAC overexpression exerted no significant effect on proliferation in this transformed cell line at any of the glucose concentrations examined. By contrast, glucose\u2010stimulated insulin secretion was impaired through a mechanism downstream of cytosolic Ca<jats:sup>2+<\/jats:sup> increases. Furthermore, glucose\u2010stimulated proinsulin biosynthesis was inhibited despite an increase in insulin transcript level. Finally, we found that glucose downregulated ZAC expression in both INS\u20101 cells and primary mouse islets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that ZAC is a negative regulator of the acute stimulatory effects of glucose on beta\u2010cells, and provide a possible explanation for both insulin deficiency in the neonate and the later relapse of diabetes in patients with transient neonatal diabetes mellitus cases. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.2325","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T18:57:09Z","timestamp":1344020229000},"page":"645-653","source":"Crossref","is-referenced-by-count":12,"title":["Overexpression of ZAC impairs glucose\u2010stimulated insulin translation and secretion in clonal pancreatic beta\u2010cells"],"prefix":"10.1002","volume":"28","author":[{"given":"Xiaoyu","family":"Du","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology McGill University Health Center Research Institute (Children's Hospital)  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houria","family":"Ounissi\u2010Benkalha","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology McGill University Health Center Research Institute (Children's Hospital)  Montreal QC 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