VITAMIN-E NORMALIZES DIACYLGLYCEROL-PROTEIN KINASE-C ACTIVATION-INDUCED BY HYPERGLYCEMIA IN RAT VASCULAR TISSUES

Hyperglycemia, a major cause of vascular complications in diabetes, ha s been shown to activate the diacylglycerol (DAG)-protein kinase C (PK C) pathway in vascular tissues, We have found that D-alpha-tocopherol (vitamin E) treatment reversed the adverse effects of hyperglycemia bo th in vitro and in vivo, In aortic smooth muscle cells (ASMCs), the PK C specific activity from the membranous fraction and total DAG were in creased by 31 +/- 4% (P < 0.05) and 50 +/- 7% (P < 0.05), respectively , when the glucose levels were changed from 5.5 to 22 mmol/l, D-alpha- tocopherol prevented the glucose-stimulated increases in DAG level and PKC activity as well as the amount of PKC beta II isoform in ASMCs cu ltured with elevated glucose levels. Comparing streptozotocin-induced diabetic rats after 2 weeks of disease to controls, specific membranou s PKC activities and total DAG levels were increased in aorta (162%, P < 0.05; 60%, P < 0.05), Intraperitoneal injection of D-alpha-tocopher ol (40 mg/kg) every other day resulted in a significant decrease of th e elevated membranous PKC specific activity and total DAG levels in pa rallel with a significant increase of D-alpha-tocopherol content in th e aorta, These findings suggested that D-alpha-tocopherol can prevent the activation of PKC in the vascular cells and aorta induced by hyper glycemia by normalizing the elevated levels of DAG.