The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Thioredoxin-interacting protein regulates insulin transcription through microRNA-204
Open accessAbstract
Beta-cell dysfunction and impaired insulin production are hallmarks of diabetes, but despite the growing diabetes epidemic, the molecular mechanisms underlying this disease have remained unclear. We identified thioredoxin-interacting protein (TXNIP), a cellular redox regulator, as a crucial factor in beta-cell biology and show that beta-cell TXNIP is upregulated in diabetes, whereas TXNIP deficiency protects against diabetes by preventing beta-cell apoptosis. Here we show that TXNIP and diabetes induce beta-cell expression of a specific microRNA, miR-204, which in turn blocks insulin production by directly targeting and downregulating MAFA, a known insulin transcription factor. In particular, we first discovered the regulation of miR-204 by TXNIP by microarray analysis, followed by validation studies in INS-1 beta cells, islets of Txnip-deficient mice, diabetic mouse models and primary human islets. We then further found that TXNIP induces miR-204 by inhibiting the activity of signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in miR-204 regulation. We also identified MAFA as a target that is downregulated by miR-204. Taken together, our results demonstrate that TXNIP controls microRNA expression and insulin production and that miR-204 is involved in beta-cell function. The newly identified TXNIP–miR-204–MAFA–insulin pathway may contribute to diabetes progression and provides new insight into TXNIP function and microRNA biology in health and disease.
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Cited by
Trends in insulin resistance: insights into mechanisms and therapeutic strategy
Li, M., Chi, X., Wang, Y., Setrerrahmane, S., Xie, W., & Xu, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01073-0 · Cited by 939
The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes
Belgardt, B.-F., Ahmed, K., Spranger, M., Latreille, M., Denzler, R., Kondratiuk, N., von Meyenn, F., Villena, F. N., Herrmanns, K., Bosco, D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3862 · Cited by 278
Verapamil and beta cell function in adults with recent-onset type 1 diabetes
Ovalle, F., Grimes, T., Xu, G., Patel, A. J., Grayson, T. B., Thielen, L. A., Li, P., & Shalev, A. (2018) · Nature Medicine · doi:10.1038/s41591-018-0089-4 · Cited by 249
Self-citationβ-Cell MicroRNAs: Small but Powerful
Filios, S. R., & Shalev, A. (2015) · Diabetes · doi:10.2337/db15-0831 · Cited by 106
Self-citationRabbani, N., Xue, M., Weickert, M. O., & Thornalley, P. J. (2021) · Nutrients · doi:10.3390/nu13072374 · Cited by 74
Metadata
- Authors
- Xu, G., Chen, J., Jing, G., & Shalev, A.
- Venue
- Nature Medicine
- Published
- 2013-08-25
- Volume
- 19
- Issue
- 9
- Pages
- 1141-1146
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1984607812
- Cited by
- 279
- References
- 41
- FWCI
- 17.66
- Type
- journal article
- Language
- en
- Open access
- green
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