[Tissular toxicity of glucose and therapeutic perspectives].
Vascular endothelial cells are the main victims of chronic hyperglycaemia. In these cells glucose uptake is directly proportional to the glucose concentration in the medium. Excessive intracellular glucose concentration increases the production of free radicals. Free radicals directly activate 4 biochemical pathways which are involved in the pathogenesis of chronic diabetic complications: the hexosamine pathway, the polyol pathway, the advanced glycation endproducts pathway and the activation of protein kinase C. A precapillary vasodilatation is consequent to the developed pseudo-hypoxia, which provides a haemodynamic basis for diabetic microangiopathy. New specific inhibitors of each of these pathways are studied in clinical trials. Based on these pathophysiological observations, a new treatment strategy is proposed for diabetic microangiopathy.
Larger
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Service de diabétologie-endocrinologie-nutrition Groupe hospitalier Bichat-Claude Bernard 75877 Paris. etienne.larger@college-de-france.fr
Marre
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D000975:Antioxidants / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D003925:Diabetic Angiopathies / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005609:Free Radicals; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013997:Time Factors
D000975:Antioxidants; D001786:Blood Glucose; D005609:Free Radicals; D005634:Fructose-Bisphosphate Aldolase; D005947:Glucose; D006442:Glycated Hemoglobin; D010088:Oxidoreductases; D011493:Protein Kinase C