The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Reduction in Pancreatic Transcription Factor PDX-1 Impairs Glucose-stimulated Insulin Secretion
Open accessAbstract
Complete lack of transcription factor PDX-1 leads to pancreatic agenesis, whereas heterozygosity for PDX-1 mutations has been recently noted in some individuals with maturity-onset diabetes of the young (MODY) and in some individuals with type 2 diabetes. To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. NAD(P)H generation in response to glucose was reduced by 30% in PDX-1(+/-) mice. The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. However, insulin secretory responses to 10 mm 2-ketoisocaproate and 20 mm KCl were significantly reduced (by 61 and 66%, respectively). These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets.
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Cites
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
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Early-onset type-ll diabetes mellitus (MODY4) linked to IPF1
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Insulin Secretion from Pancreatic B Cells Caused by L-Arginine-Derived Nitrogen Oxides
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Cited by
Brissova, M., Fowler, M. J., Nicholson, W. E., Chu, A., Hirshberg, B., Harlan, D. M., & Powers, A. C. (2005) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.5c6684.2005 · Cited by 797
Self-citationNewsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira‐Emilio, H. C., Carpinelli, A. R., & Curi, R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135871 · Cited by 684
Kitamura, T., Nakae, J., Kitamura, Y., Kido, Y., Biggs, W., Wright, C. V. E., White, M. F., Arden, K. C., & Accili, D. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16857 · Cited by 580
Self-citationInactivation 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
Self-citationDevelopmental biology of the pancreas: A comprehensive review
Gittes, G. K. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2008.10.024 · Cited by 451
Metadata
- Authors
- Brissova, M., Shiota, M., Nicholson, W. E., Gannon, M., Knobel, S. M., Piston, D. W., Wright, C. V. E., & Powers, A. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 277
- Issue
- 13
- Pages
- 11225-11232
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2026145411
- Cited by
- 375
- References
- 55
- FWCI
- 17.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Brissova, M., Shiota, M., Nicholson, W. E., Gannon, M., Knobel, S. M., Piston, D. W., Wright, C. V. E., & Powers, A. C. (2002). Reduction in Pancreatic Transcription Factor PDX-1 Impairs Glucose-stimulated Insulin Secretion. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111272200
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