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Abstract：
The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.
摘要：
糖尿病的患病率在上个世纪增加，估计有45％的患者未被诊断。在南美洲，糖尿病和慢性肾脏病（CKD）的患病率增加，各国在获得透析方面存在巨大差距。在厄瓜多尔，它是死亡的主要原因之一，主要位于太平洋沿岸的省份。开始透析的最大单一原因是糖尿病肾病(DN)。即使使用DN的最佳治疗选择，蛋白尿和终末期CKD的残余风险仍然很高。在这次审查中，我们指出了该问题在全球和我们地区的重要性。我们分析了相关的细胞和分子研究，这些研究说明了肾小球事件在DN发展和进化以及胰岛素抵抗中的重要意义。我们包括基本的解剖学，病理生理和临床概念，特别关注血管生成因子如血管内皮生长因子（VEGF-A）的作用及其与胰岛素受体的关系，一氧化氮合酶（eNOS）和血管生成素的内皮同工型。我们还提出了我们认为具有治疗潜力的各种途径。更深入的研究VEGF-A和血管生成素，肾小球VEGF抵抗的状态，VEGF受体2/nephrin的关系，VEGF/胰岛素受体/nephrin以及肾小球水平的VEGF/eNOS-NO的关系可以为DN这一紧迫的世界问题提供解决方案，并产生新的治疗替代方案。
