Transcriptional regulation of the IAPP gene in pancreatic beta-cells

L.M.A. Shepherd, S.C. Campbell, Wendy Macfarlane

Research output: Contribution to journalArticle

Abstract

Islet amyloid polypeptide (IAPP or amylin) is co-secreted with insulin from the pancreatic β-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 cytokines TNF-α, IL-1α and IL-1β 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-3β (FoxA2) negatively regulates the IAPP promoter, whilst the MODY3 transcription factor HNF-1α positively regulates promoter activity.
Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalBiochimica Et Biophysica Acta-Gene Structure and Expression
Volume1681
Issue number1
DOIs
Publication statusPublished - 24 Nov 2004

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