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首页> 外文期刊>Peritoneal dialysis international: Journal of the International Society for Peritoneal Dialysis >The role of protein kinase C activation in the pathogenesis of diabetic vascular complications.
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The role of protein kinase C activation in the pathogenesis of diabetic vascular complications.

机译:蛋白激酶C激活在糖尿病血管并发症发病机理中的作用。

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摘要

Many vascular diseases in diabetes are known to be associated with the activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway. The major source of DAG that is elevated in diabetes is de novo synthesis from glycolytic intermediates. Among the various PKC isoforms, the beta-isoform has been shown to be persistently activated in diabetic animals. Multiple lines of evidence have shown that many vascular alterations in diabetes--such as a decrease in the activity of Na+-K+-adenosine triphosphatase (Na+-K+-ATPase), and increases in extracellular matrix, cytokines, permeability, contractility, and cell proliferation--are caused by activation of PKC. Inhibition of PKC by two different kinds of PKC inhibitors, LY333531, a selective PKC-beta-isoform inhibitor, and d-alpha-tocopherol, were able to prevent or reverse the various vascular dysfunctions in diabetic rats. These results have also provided in vivo evidence that DAG-PKC activation could be responsible for the hyperglycemia-induced vascular dysfunctions in diabetes. Clinical studies are now being performed to clarify the pathogenic roles of the DAG-PKC pathway in developing vascular complications in diabetic patients.
机译:已知许多糖尿病中的血管疾病与二酰基甘油(DAG)-蛋白激酶C(PKC)途径的激活有关。在糖尿病中升高的DAG的主要来源是糖酵解中间体的从头合成。在各种PKC同工型中,β同工型已显示在糖尿病动物中被持续激活。多方面的证据表明,糖尿病患者有许多血管改变,例如Na + -K +-腺苷三磷酸酶(Na + -K + -ATPase)活性降低,以及细胞外基质,细胞因子,通透性,收缩力和细胞增多增殖-由PKC激活引起。两种不同种类的PKC抑制剂LY333531(一种选择性的PKC-β亚型抑制剂和d-α-生育酚)对PKC的抑制作用能够预防或逆转糖尿病大鼠的各种血管功能障碍。这些结果也提供了体内证据,表明DAG-PKC激活可能是糖尿病引起的高血糖引起的血管功能障碍的原因。现在正在进行临床研究,以阐明DAG-PKC途径在糖尿病患者发生血管并发症中的致病作用。

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