Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10767970 | Biochemical and Biophysical Research Communications | 2005 | 9 Pages |
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.
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Authors
Alexandra H. Minn, Cynthia A. Pise-Masison, Michael Radonovich, John N. Brady, Ping Wang, Christina Kendziorski, Anath Shalev,