Nordquist Lina, Palm Fredrik
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Curr Diabetes Rev. 2007 Feb;3(1):53-65. doi: 10.2174/157339907779802120.
Diabetes-induced renal complications, i.e. diabetes nephropathy, are a major cause of morbidity and mortality. The exact mechanisms mediating the negative influence of hyperglycemia on renal function are unclear, although several hypotheses have been postulated. Cellular mechanisms include glucose-induced excessive formation of reactive oxygen species, increased glucose flux through polyol pathway and pentose phosphate shunt, formation of advanced glycation end-products and activation of protein kinase C and NADPH oxidase. However, the renal effects in vivo of each and every one of these mechanisms are less clear, although recent studies have shown several major alterations predominantly in the renal medulla as a result of sustained hyperglycemia. Already during normal conditions, the renal medulla has a remarkably low oxygen tension (PO2) and a high degree of non-oxygen dependent energy metabolism. Alterations in either blood perfusion or oxygen delivery to the medullary region will have significant effects on both regional metabolism and total kidney function. Recently, sustained hyperglycemia has been shown to induce a pronounced reduction in preferentially renal medullary PO2. This review will present the current knowledge of diabetes-induced alterations in renal medullary metabolism and function, but also discuss future targets for prevention of diabetic nephropathy.
糖尿病引发的肾脏并发症，即糖尿病肾病，是发病和死亡的主要原因。尽管已经提出了几种假说，但介导高血糖对肾功能产生负面影响的确切机制尚不清楚。细胞机制包括葡萄糖诱导的活性氧过度生成、通过多元醇途径和磷酸戊糖旁路的葡萄糖通量增加、晚期糖基化终产物的形成以及蛋白激酶C和NADPH氧化酶的激活。然而，尽管最近的研究表明，由于持续高血糖，主要在肾髓质出现了一些重大改变，但这些机制中每一种在体内对肾脏的影响仍不太清楚。在正常情况下，肾髓质的氧张力（PO2）就显著较低，且具有高度的非氧依赖性能量代谢。髓质区域的血液灌注或氧输送的改变都会对区域代谢和整体肾功能产生重大影响。最近的研究表明，持续高血糖会导致肾髓质PO2明显降低。本综述将介绍目前关于糖尿病引起的肾髓质代谢和功能改变的知识，同时也将讨论预防糖尿病肾病的未来靶点。
