Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in Diabetes*

@article{Robertson2004ChronicOS,
  title={Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in Diabetes*},
  author={R. Paul Robertson},
  journal={Journal of Biological Chemistry},
  year={2004},
  volume={279},
  pages={42351 - 42354}
}
  • R. Robertson
  • Published 8 October 2004
  • Chemistry, Medicine
  • Journal of Biological Chemistry
Glucose in chronic excess causes toxic effects on structure and function of organs, including the pancreatic islet. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might… 
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References

SHOWING 1-10 OF 55 REFERENCES
A role for glutathione peroxidase in protecting pancreatic β cells against oxidative stress in a model of glucose toxicity
TLDR
The hypothesis that oxidative stress is one mechanism for glucose toxicity in pancreatic islets is supported by observations that glucose and ribose increase islet peroxide accumulation and that the adverse consequences of ribose-induced oxidative stress on insulin mRNA, content, and secretion can be augmented by a glutathione synthesis inhibitor and prevented by increasing islet GPx activity.
Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants.
TLDR
It is concluded that chronic oxidative stress may play a role in glucose toxicity, which in turn may worsen the severity of type 2 diabetes.
Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity.
TLDR
Observations indicate that antioxidant treatment can exert beneficial effects in diabetes, with preservation of in vivo beta- cell function, and provides further support for the implication of oxidative stress in beta-cell dysfunction in diabetes.
Glucose-induced oxidative stress in mesangial cells.
TLDR
The results demonstrate the existence of glucose-induced oxidative stress in mesangial cells as evidenced by elevated MDA and decreased GSH levels.
d-Glyceraldehyde Causes Production of Intracellular Peroxide in Pancreatic Islets, Oxidative Stress, and Defective Beta Cell Function via Non-mitochondrial Pathways*
TLDR
Observations indicate that exposure to excess d-GLYC increases reactive oxygen species in the islet via non-mitochondrial pathways and suggest the hypothesis that the oxidative stress associated with elevated d- GLYC levels could be a mechanism for glucose toxicity in beta cells exposed chronically to high glucose concentrations.
Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic β-Cell Function through the Induction of Oxidative Stress*
TLDR
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.
Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic β-cells
TLDR
It is demonstrated that mitochondrial ROS suppress glucose-induced insulin secretion (GIIS) from beta-cells, and proposed that mitochondrial overwork is a potential mechanism causing impaired first-phase of GIIS in the early stages of diabetes mellitus.
High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program.
TLDR
Comparing the effect of 5 days' culture in high glucose concentration versus normal glucose levels or hyperosmolar control on the survival of human pancreatic islets suggests that in human islets, high glucose may modulate the balance of proapoptotic and antiap optotic Bcl proteins toward apoptosis, thus favoring beta-cell death.
Impaired beta-cell functions induced by chronic exposure of cultured human pancreatic islets to high glucose.
TLDR
It is concluded that cultured human islets are sensitive to the deleterious effect of high glucose concentrations at multiple functional levels, and that such mechanisms may play an important role in the decreased insulin production and secretion of type 2 diabetic patients.
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