The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Thioredoxin-Interacting Protein Is Stimulated by Glucose through a Carbohydrate Response Element and Induces β-Cell Apoptosis
Open accessAbstract
Recently, we identified thioredoxin-interacting protein (TXNIP) as the most dramatically glucose-induced gene in our human islet microarray study. TXNIP is a regulator of the cellular redox state, but its role in pancreatic beta-cells and the mechanism of its regulation by glucose remain unknown. We therefore generated a stable transfected beta-cell line (INS-1) overexpressing human TXNIP and found that TXNIP overexpression induced apoptosis as assessed by Bax, Bcl2, caspase-3, and cleaved caspase-9 as well as Hoechst staining. Interestingly, islets of insulin-resistant/diabetic mice (AZIP-F1, BTBRob/ob) demonstrated elevated TXNIP expression, suggesting that TXNIP may play a role in glucotoxicity and the beta-cell loss observed under these conditions. Furthermore, we found that glucose-induced TXNIP transcription is not dependent on glucose metabolism and is mediated by a distinct carbohydrate response element (ChoRE) in the human TXNIP promoter consisting of a perfect nonpalindromic repeat of two E-boxes. Transfection studies demonstrated that this ChoRE was necessary and sufficient to confer glucose responsiveness. Thus, TXNIP is a novel proapoptotic beta-cell gene elevated in insulin resistance/diabetes and up-regulated by glucose through a unique ChoRE and may link glucotoxicity and beta-cell apoptosis.
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Cites
Glucose Toxicity in β-Cells: Type 2 Diabetes, Good Radicals Gone Bad, and the Glutathione Connection
Robertson, R. P., Harmon, J., Tran, P. O., Tanaka, Y., & Takahashi, H. (2003) · Diabetes · doi:10.2337/diabetes.52.3.581 · Cited by 897
Poitout, V., & Robertson, R. P. (2002) · Endocrinology · doi:10.1210/endo.143.2.8623 · Cited by 743
Pick, A., Clark, J., Kubstrup, C., Levisetti, M., Pugh, W., Bonner-Weir, S., & Polonsky, K. S. (1998) · Diabetes · doi:10.2337/diabetes.47.3.358 · Cited by 551
Cited by
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708
Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses
Papadia, S., Soriano, F. X., Léveillé, F., Martel, M.-A., Dakin, K. A., Hansen, H. H., Kaindl, A., Sifringer, M., Fowler, J., Stefovska, V., et al. (2008) · Nature Neuroscience · doi:10.1038/nn2071 · Cited by 498
TXNIP regulates peripheral glucose metabolism in humans
Parikh, H., Carlsson, E., Chutkow, W. A., Johansson, L. E., Storgaard, H., Poulsen, P., Saxena, R., Ladd, C., Schulze, P. C., Mazzini, M. J., et al. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040158 · Cited by 495
Stoltzman, C. A., Peterson, C. W., Breen, K. T., Muoio, D. M., Billin, A. N., & Ayer, D. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712199105 · Cited by 283
Ivarsson, R., Quintens, R., Dejonghe, S., Tsukamoto, K., in ’t Veld, P., Renström, E., & Schuit, F. C. (2005) · Diabetes · doi:10.2337/diabetes.54.7.2132 · Cited by 265
Metadata
- Authors
- Minn, A. H., Hafele, C., & Shalev, A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-05
- Volume
- 146
- Issue
- 5
- Pages
- 2397-2405
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2061741332
- Cited by
- 367
- References
- 3
- FWCI
- 14.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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