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Transcriptional regulation of the IAPP gene in pancreatic beta-cells

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.

Publication metadata

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


DOI: 10.1016/j.bbaexp.2004.09.009


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