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Updated: Aug 20, 2026

A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
Transcriptional regulation of the IAPP gene in pancreatic beta-cells
Louisa M A Shepherd1, Susan C Campbell, Wendy M Macfarlane
1School of Cell and Molecular Biosciences, University of Newcastle upon Tyne, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Abstract:
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 cytokines TNF-alpha, IL-1alpha 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.
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