Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein

Academic Article

Abstract

  • Thioredoxin-interacting protein (TXNIP) is overexpressed in diabetes and has deleterious effects on pancreatic β-cells and the cardiovascular system. TXNIP is a regulator of the cellular redox state, but has also been suggested to act as a transcriptional repressor. However, the genes and pathways regulated by TXNIP remain unknown. We therefore compared gene expression in INS-1 insulinoma β-cells overexpressing TXNIP and control LacZ-overexpressing cells using the Affymetrix 230A rat chip. Analysis with the Bayes methodology revealed 98 differentially expressed genes, 90 of which were down-regulated, consistent with the predicted role of TXNIP as a repressor. Using the PathwayAssist software, we found that affected genes were involved in cell death/survival and insulin secretion, and confirmed these findings by real-time RT-PCR and by functional studies. Thus, aside from regulating the cellular redox, TXNIP does modulate overall gene transcription and thereby may further enhance β-cell death and impair insulin secretion. © 2005 Elsevier Inc. All rights reserved.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Minn AH; Pise-Masison CA; Radonovich M; Brady JN; Wang P; Kendziorski C; Shalev A
  • Start Page

  • 770
  • End Page

  • 778
  • Volume

  • 336
  • Issue

  • 3