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Scientific article
English

Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets

Contributors

Bergholdt, R; Karlsen, A E; Hagedorn, P H; Aalund, M; Nielsen, J H; Kruhøffer, M; Orntoft, T; Wang, Haiyan; Wollheim, Claes; Nerup, J; Pociot, F

Published in

Genes and immunity, vol. 8, no. 3, p. 232-238

Publication date

2007

Abstract

We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1alphabeta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1beta (IL-1beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.

Keywords

  • Adolescent
  • Adult
  • Animals
  • Cell Line, Tumor
  • Child
  • Chromosomes, Human, Pair 21/genetics
  • Diabetes Mellitus, Type 1/genetics
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Homeodomain Proteins/genetics
  • Humans
  • Insulin-Secreting Cells/drug effects/metabolism
  • Insulinoma/genetics
  • Interleukin-1beta/pharmacology
  • Islets of Langerhans/drug effects/metabolism
  • Male
  • Middle Aged
  • Pancreatic Neoplasms/genetics
  • Rats
  • Trans-Activators/genetics

UNIGE affiliation entities

Citation (ISO format)

BERGHOLDT, R et al. Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets. In: Genes and immunity, 2007, vol. 8, n° 3, p. 232–238. doi: 10.1038/sj.gene.6364379

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

1466-4879
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Technical informations

Creation

20/01/2014 11:57:00

First validation

20/01/2014 11:57:00

Update

14/03/2023 20:52:19

Status update

14/03/2023 20:52:18

Last indexation

30/10/2024 15:57:00
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