Kunisaki M, Fumio U, Nawata H, King G L
Research Division, Joslin Diabetes Center, Boston, Massachusetts, 02215, USA.
Diabetes. 1996 Jul;45 Suppl 3:S117-9. doi: 10.2337/diab.45.3.s117.
Hyperglycemia, a major cause of vascular complications in diabetes, has been shown to activate the diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular tissues. We have found that D-alpha-tocopherol (vitamin E) treatment reversed the adverse effects of hyperglycemia both in vitro and in vivo. In aortic smooth muscle cells (ASMCs), the PKC specific activity from the membranous fraction and total DAG were increased 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 cultured with elevated glucose levels. Comparing streptozotocin-induced diabetic rats after 2 weeks of disease to controls, specific membranous PKC activities and total DAG levels were increased in aorta (162%, P < 0.05; 60%, P < 0.05). Intraperitoneal injection of D-alpha-tocopherol (40 mg/kg) every other day resulted in a significant decrease of the elevated membranous PKC specific activity and total DAG levels in parallel with a significant increase of D-alpha-tocopherol content in the aorta. These findings suggested that D-alpha-tocopherol can prevent the activation of PKC in the vascular cells and aorta induced by hyperglycemia by normalizing the elevated levels of DAG.
高血糖是糖尿病血管并发症的主要原因，已被证明可激活血管组织中的二酰甘油（DAG）-蛋白激酶C（PKC）途径。我们发现，D-α-生育酚（维生素E）治疗可在体外和体内逆转高血糖的不良影响。在主动脉平滑肌细胞（ASMCs）中，当葡萄糖水平从5.5 mmol/l变为22 mmol/l时，膜组分中的PKC比活性和总DAG分别增加了31±4%（P<0.05）和50±7%（P<0.05）。D-α-生育酚可防止葡萄糖刺激的ASMCs中DAG水平、PKC活性以及PKCβII同工型数量的增加，这些细胞是在高葡萄糖水平下培养的。将链脲佐菌素诱导的糖尿病大鼠患病2周后与对照组进行比较，主动脉中的膜PKC比活性和总DAG水平增加（分别为162%，P<0.05；60%，P<0.05）。每隔一天腹腔注射D-α-生育酚（40 mg/kg）可使升高的膜PKC比活性和总DAG水平显著降低，同时主动脉中D-α-生育酚含量显著增加。这些发现表明，D-α-生育酚可通过使升高的DAG水平正常化来防止高血糖诱导的血管细胞和主动脉中PKC的激活。
