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Glucose and reactive oxygen species
Dominique Bonnefont-Rousselot1
1Laboratoire de Biochimie Métabolique et Clinique, Faculté de Pharmacie; and Laboratoire de Biochimie B, Hôpital de la Salpêtrière, Paris, France. dominique.rousselot@pls.ap-hop-paris.fr
Purpose Of Review:
This review aims at presenting new concepts of glucose-induced damage in diabetes via an increased production of oxygen free radicals.
Recent Findings:
Reactive oxygen species modulate various biological functions by stimulating transduction signals, some of which are involved in diabetes pathogenesis and complications.
Summary:
Diabetes is characterized by high glucose concentrations that lead, via several mechanisms (glucose autoxidation, stimulation of the polyol pathway, activation of the reduced form of nicotinamide adenine dinucleotide phosphate oxidase, and production of advanced glycation endproducts), to an increased production of reactive oxygen species. The resulting oxidative stress (the imbalance between reactive oxygen species production and the antioxidant defences) can play a key role in diabetes pathogenesis. Superoxide radicals generated by the reduced form of nicotinamide adenine dinucleotide phosphate oxidase may thus contribute to impaired endothelium-dependent vascular relaxation by the inactivation of nitric oxide, and more generally to vascular dysfunction, thereby contributing to accelerated atherosclerosis in diabetic patients. The increased production of reactive oxygen species induced by hyperglycaemia has also been suggested to be involved in platelet dysfunction, in tissue remodelling (via metalloproteinases), and in redox regulation of glucose transport in skeletal muscle. Beyond the classic treatments for diabetes, new therapeutic strategies involving antioxidants or anti-advanced glycation endproduct molecules are proposed. Future methods could take into account the signalling pathways and genes that are regulated by reactive oxygen species.
Insights
High glucose in diabetes increases oxygen free radicals, leading to oxidative stress and complications. New antioxidant therapies targeting these mechanisms are being explored for diabetes treatment.
Area of Science:
- Biochemistry
- Endocrinology
- Pathophysiology
Background:
- Diabetes mellitus is a metabolic disorder characterized by hyperglycemia.
- Hyperglycemia triggers increased production of reactive oxygen species (ROS).
- ROS play a significant role in the pathogenesis and complications of diabetes.
Purpose of the Study:
- To review novel concepts of glucose-induced cellular damage in diabetes.
- To elucidate the role of increased oxygen free radical production in diabetes.
- To discuss emerging therapeutic strategies targeting oxidative stress in diabetes.
Main Methods:
- Literature review of studies on glucose metabolism and oxidative stress.
- Analysis of mechanisms linking hyperglycemia to ROS production.
- Synthesis of findings on the role of ROS in diabetes complications.
Main Results:
- Hyperglycemia induces ROS via multiple pathways including glucose autoxidation, polyol pathway, NADPH oxidase, and AGEs.
- Oxidative stress resulting from ROS imbalance is implicated in diabetes pathogenesis.
- ROS contribute to vascular dysfunction, impaired vasorelaxation, platelet dysfunction, and altered glucose transport.
Conclusions:
- Increased ROS production is a key mechanism of glucose-induced damage in diabetes.
- Oxidative stress contributes significantly to diabetes complications like atherosclerosis.
- Future therapeutic strategies may focus on antioxidants and targeting ROS-regulated pathways.