The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
The MODY1 gene HNF-4α regulates selected genes involved in insulin secretion
Open accessAbstract
Mutations in the gene encoding hepatocyte nuclear factor-4alpha (HNF-4alpha) result in maturity-onset diabetes of the young (MODY). To determine the contribution of HNF-4alpha to the maintenance of glucose homeostasis by the beta cell in vivo, we derived a conditional knockout of HNF-4alpha using the Cre-loxP system. Surprisingly, deletion of HNF-4alpha in beta cells resulted in hyperinsulinemia in fasted and fed mice but paradoxically also in impaired glucose tolerance. Islet perifusion and calcium-imaging studies showed abnormal responses of the mutant beta cells to stimulation by glucose and sulfonylureas. These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2. We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha. Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel.
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Hayhurst, G. P., Lee, Y.-H., Lambert, G., Ward, J. M., & Gonzalez, F. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1393-1403.2001 · Cited by 1,107
Parviz, F., Matullo, C., Garrison, W. D., Savatski, L., Adamson, J. W., Ning, G., Kaestner, K. H., Rossi, J. M., Zaret, K. S., & Duncan, S. A. (2003) · Nature Genetics · doi:10.1038/ng1175 · Cited by 588
Self-citationDefective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
Pontoglio, M., Sreenan, S., Roe, M., Pugh, W., Ostrega, D., Doyen, A., Pick, A. J., Baldwin, A., Velho, G., Froguel, P., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2548 · Cited by 321 · cited 1×
“For example, disruption of HNF-1α in mice results in defective glucose sensing and the failure of isolated islets from these animals to properly respond to glucose (21, 22).”
Background
Cited by
Pathophysiology of diabetes: An overview
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Gunton, J. E., Kulkarni, R. N., Yim, S., Okada, T., Hawthorne, W. J., Tseng, Y.-H., Roberson, R. S., Ricordi, C., O’Connell, P. J., Gonzalez, F. J., et al. (2005) · Cell · doi:10.1016/j.cell.2005.05.027 · Cited by 492
Congenital hyperinsulinism: current trends in diagnosis and therapy
Arnoux, J.-B., Verkarre, V., Saint-Martin, C., Montravers, F., Brassier, A., Valayannopoulos, V., Brunelle, F., Fournet, J.-C., Robert, J.-J., Aigrain, Y., et al. (2011) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-6-63 · Cited by 361
Sandovici, I., Smith, N. H., Nitert, M. D., Ackers-Johnson, M., Uribe-Lewis, S., Ito, Y., Jones, R. H., Marquez, V. E., Cairns, W., Tadayyon, M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019007108 · Cited by 326
Nuclear receptors: Decoding metabolic disease
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Metadata
- Authors
- Gupta, R. K., Vatamaniuk, M. Z., Lee, C. S., Flaschen, R. C., Fulmer, J. T., Matschinsky, F. M., Duncan, S. A., & Kaestner, K. H.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-03-03
- Volume
- 115
- Issue
- 4
- Pages
- 1006-1015
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2069271978
- Cited by
- 240
- References
- 3
- FWCI
- 14.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Gupta, R. K., Vatamaniuk, M. Z., Lee, C. S., Flaschen, R. C., Fulmer, J. T., Matschinsky, F. M., Duncan, S. A., & Kaestner, K. H. (2005). The MODY1 gene HNF-4α regulates selected genes involved in insulin secretion. Journal of Clinical Investigation. https://doi.org/10.1172/jci200522365
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
