Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic β-Cell Function through the Induction of Oxidative Stress*
@article{Kaneto2001ActivationOT, title={Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic β-Cell Function through the Induction of Oxidative Stress*}, author={H. Kaneto and G. Xu and K. H. Song and K. Suzuma and S. Bonner-Weir and A. Sharma and G. Weir}, journal={The Journal of Biological Chemistry}, year={2001}, volume={276}, pages={31099 - 31104} }
It is known well that activation of the hexosamine pathway causes insulin resistance, but how this activation influences pancreatic β-cell function remains unclear. In this study, we found that in isolated rat islets adenovirus-mediated overexpression of glutamine:fructose-6-phosphate amidotransferase (GFAT), the first and rate-limiting enzyme of the hexosamine pathway, leads to deterioration of β-cell function, which is similar to that found in diabetes. Overexpression of GFAT or treatment… CONTINUE READING
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References
SHOWING 1-10 OF 43 REFERENCES
Glucose stimulates protein modification by O-linked GlcNAc in pancreatic β cells: Linkage of O-linked GlcNAc to β cell death
- Biology
- 2000
- 206
- PDF
Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance.
- Chemistry, Biology
- The Journal of clinical investigation
- 1996
- 314
- PDF
Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells.
- Biology, Medicine
- The Journal of clinical investigation
- 1997
- 304
- PDF
Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle.
- Biology, Medicine
- Diabetes
- 1999
- 245
Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants.
- Biology, Medicine
- Proceedings of the National Academy of Sciences of the United States of America
- 1999
- 425
- PDF
Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation.
- Biology, Medicine
- Proceedings of the National Academy of Sciences of the United States of America
- 2000
- 984
- PDF
Transgenic mice with increased hexosamine flux specifically targeted to beta-cells exhibit hyperinsulinemia and peripheral insulin resistance.
- Biology, Medicine
- Diabetes
- 2000
- 74
- PDF
Role of the glucosamine pathway in fat-induced insulin resistance.
- Biology, Medicine
- The Journal of clinical investigation
- 1997
- 298
- PDF
Increased O-GlcNAc transferase in pancreas of rats with streptozotocin-induced diabetes
- Biology, Medicine
- Diabetologia
- 2000
- 55
- PDF
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
- Biology, Chemistry
- Nature
- 2000
- 3,844