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 . 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 . 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 Diabetes-related activation of DAG-PKC pathway in vascular cells and tissues. 190 .
