Đang chuẩn bị liên kết để tải về tài liệu:
VASCULAR COMPLICATIONS OF DIABETES - PART 9

Nó bây giờ là nhận ra rằng kích hoạt protein kinase C (PKC) theo điều kiện của tăng đường huyết là một trong những cơ chế chủ yếu của tổn thương mạch máu ở những bệnh nhân bị bệnh tiểu đường. Được vận chuyển glucose vào các tế bào mạch máu bởi thị trường bất động-1 vận chuyển và sau đó chuyển hóa, | Vascular Complications of Diabetes Current Issues in Pathogenesis and Treatment Second Edition Edited by Richard Donnelly Edward Horton Copyright 2005 by Blackwell Publishing Ltd CHAPTER 21 PROTEIN KINASE C Richard Donnelly MD PhD FRCP FRACP 189 INTRODUCTION It is now recognized that activation of protein kinase C PKC under conditions of hyperglycaemia is one of the principal mechanisms of vascular damage in patients with diabetes. Glucose is transported into vascular cells by GLUT-1 transporters and then metabolized mostly via glycolysis 5 is metabolized by the aldose reductase polyol pathway even under conditions of hyperglycaemia . GLUT-1 expression in vascular cells is up-regulated by high extracellular glucose concentrations and other local factors involved in diabetic angiopathy e.g. hypoxia. The increase in glycolysis results in increased de novo synthesis of diacylglycerol DAG which is the main endogenous activator of a ubiquitous intracellular enzyme known as PKC. Several studies have shown both in animals and humans with diabetes that there is a widespread increase in DAG levels and PKC activity in different types of vascular cell Table 21.1 . PROTEIN KINASE C PKC A MULTIFUNCTIONAL FAMILY OF ISOENZYMES It has long been recognized that adding and removing phosphate groups is one of the most important physiological mechanisms by which the activity Diabetes-related activation of DAG-PKC pathway in vascular cells and tissues Species DAG Content PKC Activity Isoforms Activated Cells in culture Aortic Endothelial Rat bovine 1 1 p Aortic VSM Rat human 1 1 -p Retinal Endothelial Bovine 1 1 -piI -Ô Retinal Pericytes Bovine NM 1 -pii -Ô Renal mesangial Rat 1 1 -a pi Renal glomerular Rat 1 1 -a pi Tissues Heart Rat human 1 1 -p -E Retina Rat canine 1 1 -pii Ô Aorta Rat canine 1 1 -p Glomeruli Rat mouse 1 1 -Ỗ -pi -a Monocytes Human NM 1 -pII 1 increased NM not measured Table 21.1 Diabetes-related activation of DAG-PKC pathway in vascular cells and tissues. 190 .