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Negative consequences of glycation
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abstract:
The Diabetes Control and Complications Trial (DCCT) established unequivocally that the effects of inadequate insulin action (as monitored by the level of hyperglycemia) are associated with the incidence and progression of diabetic retinopathy, nephropathy, and neuropathy. How does hyperglycemia induce the functional and morphologic changes that characterize diabetic complications? Increasing evidence points to a major role for sugar-derived advanced glycation end products (AGEs), which form inside and outside cells as a function of glucose concentration. Recent work in this area supports a central role for reactive oxygen species (ROS) in both the formation of AGEs, and in AGE-induced pathologic alterations in gene expression. Inhibition of ROS may also be centrally important in the action of drugs that prevent complications in diabetic animal models.
Insights
High blood sugar (hyperglycemia) drives diabetic complications like retinopathy and neuropathy. Advanced glycation end products and reactive oxygen species are key contributors to these damaging effects.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Molecular Biology
Background:
- The Diabetes Control and Complications Trial (DCCT) linked hyperglycemia to diabetic complications.
- Diabetic complications include retinopathy, nephropathy, and neuropathy.
- The mechanisms by which hyperglycemia causes these complications are under investigation.
Purpose of the Study:
- To explore the role of hyperglycemia in the development of diabetic complications.
- To investigate the involvement of advanced glycation end products (AGEs) and reactive oxygen species (ROS) in these processes.
Main Methods:
- Review of existing evidence on hyperglycemia, AGEs, and ROS in diabetes.
- Analysis of the formation and cellular effects of AGEs.
- Examination of the role of ROS in AGE formation and AGE-induced gene expression changes.
Main Results:
- Hyperglycemia is strongly associated with the incidence and progression of diabetic complications.
- Advanced glycation end products (AGEs) form as a function of glucose concentration and play a major role.
- Reactive oxygen species (ROS) are implicated in both AGE formation and AGE-induced pathological gene expression alterations.
Conclusions:
- AGEs are central mediators of hyperglycemia-induced diabetic complications.
- ROS play a critical role in AGE formation and subsequent cellular damage.
- Inhibiting ROS may be a therapeutic strategy for preventing diabetic complications, as suggested by animal models.