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Lookup NU author(s): Louisa Shepherd, Dr Susan Campbell
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Islet amyloid polypeptide (IAPP or amylin) is co-secreted with insulin from the pancreatic beta-cells. Transcription of the IAPP gene is controlled by a complex promoter region, spanning from -2798 to +450 relative to the transcriptional start site. In the present study, we have used reporter gene analysis and semi-quantitative RT-PCR to establish that insulin, glucagon, glucagon-like peptide-1 (GLP-1) and the GLP-1 derivatives GLP(7-36)Amide and Exendin-4 all stimulate IAPP promoter activity, as well as endogenous IAPP mRNA levels in isolated islets of Langerhans. In contrast, somatostatin had no effect, and whilst the inflammatory cyrokines TNF-alpha, IL-1beta and IL-1beta had no effect on promoter activity, they all decreased IAPP mRNA levels in isolated islets. Finally, utilising a series of deletion reporter gene constructs of the human IAPP gene promoter, we used overexpression studies to establish that HNF-3beta (FoxA2) negatively regulates the IAPP promoter, whilst the MODY3 transcription factor HNF-1alpha positively regulates promoter activity. (C) 2004 Elsevier B.V. All rights reserved.
Author(s): Shepherd LMA, Campbell SC, Macfarlane WM
Publication type: Article
Publication status: Published
Journal: Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression
Year: 2004
Volume: 1681
Issue: 1
Pages: 28-37
ISSN (print): 0167-4781
ISSN (electronic):
Publisher: Elsevier BV
URL: http://dx.doi.org/10.1016/j.bbaexp.2004.09.009
DOI: 10.1016/j.bbaexp.2004.09.009
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