Hepatocyte nuclear factor 1 negatively regulates amylin gene expression

Janelle Green, Dorit Naot, Garth Cooper

Research output: Contribution to journalArticlepeer-review

Abstract

Maturity-onset diabetes of the young (MODY) is a monogenic subtype of Type 2 diabetes, defined as having an early age of onset, with a dominant inheritance pattern. Hepatocyte nuclear factor 1 (HNF1), which is encoded by the MODY3 gene, has been shown to bind the insulin promoter. Since the promoters of three pancreas-specific genes involved in glucose homeostasis-insulin, glucokinase, and amylin bind similar transcription factors, we were interested in whether HNF1 could also regulate amylin expression. In the present study, we used the electrophoretic mobility shift assay, to demonstrate that the HNF1 transcription factor can specifically bind to the amylin promoter. Moreover, co-transfection of an HNF1 expression vector with an amylin-CAT reporter plasmid decreased the activity of the amylin promoter by 85%. These data support the hypothesis that the amylin gene is regulated by HNF1 in a negative manner and may explain partially how HNF1 mutations result in diabetes. © 2003 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)464-469
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume310
Issue number2
DOIs
Publication statusPublished - 17 Oct 2003

Keywords

  • Amylin
  • Hepatocyte nuclear factor 1
  • Islet amyloid polypeptide
  • Maturity-onset diabetes of the young
  • Maturity-onset diabetes of the young 3
  • Transcriptional regulation
  • Type 2 diabetes

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