BIOCHEMISTRY OF HYPERGLYCEMIA INDUCED VASCULAR DYSFUNCTION

Abstract

Glucose enters the endothelium via a non-insulin sensitive GLUT-1 facilitated transporter that transports glucose continuously. Extracellular hyperglycemia is positively correlated with intracellular glucose. As the glucose levels increase, several changes in the glycolytic pathway, tricarboxilic acid cycle and the pentose phosphate pathway occur, all of them leading to an increase of oxygen reactive species (ROS). ROS are capable not only of directly impairing endothelial cells, but also indirectly by activating poly(ADP- ribose) polymerase, which inhibits glyceraldehyde 3-phosphate dehydrogenase. Further increase in glycloytic intermediates is followed by activation or overexpression of the main pathological pathways of hyperglycemia induced vascular damage: upregulation of glycation end-products, activation of protein kinase C, increased hexosamine pathway, and increased flux through polyol pathway, finally leading to the progressive narrowing and occlusion of the vessels.