Abstract:
BACKGROUND:ZAC (Zinc finger protein that regulates apoptosis and cell-cycle 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-cell mass and possibly function. The present study therefore aimed to examine the role of ZAC in beta-cell function in vitro, independent of the confounder of a reduced beta-cell mass at birth. METHODS:Overexpression of ZAC was achieved through the tetracycline-regulatable system in the beta-cell line, INS-1. RESULTS: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-stimulated insulin secretion was impaired through a mechanism downstream of cytosolic Ca(2+) increases. Furthermore, glucose-stimulated proinsulin biosynthesis was inhibited despite an increase in insulin transcript level. Finally, we found that glucose downregulated ZAC expression in both INS-1 cells and primary mouse islets. CONCLUSIONS:These results indicate that ZAC is a negative regulator of the acute stimulatory effects of glucose on beta-cells, 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.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Du X,Ounissi-Benkalha H,Loder MK,Rutter GA,Polychronakos Cdoi
10.1002/dmrr.2325subject
Has Abstractpub_date
2012-11-01 00:00:00pages
645-53issue
8eissn
1520-7552issn
1520-7560journal_volume
28pub_type
杂志文章abstract:BACKGROUND:For cost-effective population-based diabetes prediction and confirmation, islet autoantibody assays must be made more economical. METHODS:We evaluated glutamic acid decarboxylase (GAD)-Ruc (renilla luciferase) and IA2ic (also known as ICA512ic)-Ruc (renilla luciferase) fusion protein constructs in high-thro...
journal_title:Diabetes/metabolism research and reviews
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pub_type: 杂志文章,评审
doi:10.1002/dmrr.2703
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更新日期:2017-01-01 00:00:00
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journal_title:Diabetes/metabolism research and reviews
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doi:10.1002/1520-7560(2000)9999:9999<::aid-dmrr148>3.0
更新日期:2000-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/dmrr.727
更新日期:2007-09-01 00:00:00
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更新日期:2011-10-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2004-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/dmrr.3068
更新日期:2019-01-01 00:00:00
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doi:10.1002/dmrr.3230
更新日期:2020-02-01 00:00:00
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更新日期:2007-07-01 00:00:00
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更新日期:2015-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2014-10-01 00:00:00
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更新日期:2019-11-01 00:00:00
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更新日期:1999-09-01 00:00:00
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更新日期:2014-01-01 00:00:00
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更新日期:2020-03-01 00:00:00
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