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MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion
Open accessAbstract
MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis. To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice. Here we report that MafA mutant mice display intolerance to glucose and develop diabetes mellitus. Detailed analyses revealed that glucose-, arginine-, or KCl-stimulated insulin secretion from pancreatic beta cells is severely impaired, although insulin content per se is not significantly affected. MafA-deficient mice also display age-dependent pancreatic islet abnormalities. Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice. These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
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Cited by
Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., Young, H., Richardson, M., Smart, N. G., Cunningham, J., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1393 · Cited by 1,843
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., O'Dwyer, S., Quiskamp, N., Mojibian, M., Albrecht, T., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.3033 · Cited by 1,575
Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes
Fu, Z., R. Gilbert, E., & Liu, D. (2013) · Current Diabetes Reviews · doi:10.2174/157339913804143225 · Cited by 732
Pancreas organogenesis: From bud to plexus to gland
Pan, F. C., & Wright, C. (2011) · Developmental Dynamics · doi:10.1002/dvdy.22584 · Cited by 614
Inactivation of specific β cell transcription factors in type 2 diabetes
Guo, S., Dai, C., Guo, M., Taylor, B., Harmon, J. S., Sander, M., Robertson, R. P., Powers, A. C., & Stein, R. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65390 · Cited by 520
Metadata
- Authors
- Zhang, C., Moriguchi, T., Kajihara, M., Esaki, R., Harada, A., Shimohata, H., Oishi, H., Hamada, M., Morito, N., Hasegawa, K., Kudo, T., Engel, J. D., Yamamoto, M., & Takahashi, S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-06
- Volume
- 25
- Issue
- 12
- Pages
- 4969-4976
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2132981332
- Cited by
- 488
- References
- 0
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, C., Moriguchi, T., Kajihara, M., Esaki, R., Harada, A., Shimohata, H., Oishi, H., Hamada, M., Morito, N., Hasegawa, K., Kudo, T., Engel, J. D., Yamamoto, M., & Takahashi, S. (2005). MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.25.12.4969-4976.2005
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