Sarafidis Pantelis A, Ruilope Luis M
Hypertension/Clinical Research Center, Department of Preventive Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
Am J Nephrol. 2006;26(3):232-44. doi: 10.1159/000093632. Epub 2006 May 29.
Most of the basic components of the metabolic syndrome, namely type 2 diabetes mellitus, hypertension, obesity, or low high-density lipoprotein cholesterol levels, apart from being major risk factors for cardiovascular disease have been also associated with an increased risk of chronic kidney disease. However, several epidemiologic studies conducted over the past years suggest that the central component of the syndrome, insulin resistance, as well as compensatory hyperinsulinemia are independently associated with an increased prevalence of chronic kidney disease. In addition, background studies support the existence of several pathways linking insulin resistance and hyperinsulinemia with kidney damage. Insulin per se promotes the proliferation of renal cells and stimulates the production of other important growth factors such as insulin-like growth factor-1 and transforming growth factor beta. Insulin also upregulates the expression of angiotensin II type 1 receptor in mesangial cells, thus enhancing the deleterious effects of angiotensin II in the kidney, and stimulates production and renal action of endothelin-1. Moreover, insulin resistance and hyperinsulinemia are associated with decreased endothelial production of nitric oxide and increased oxidative stress which have been also implicated in the progression of diabetic nephropathy. This review analyzes the above and other potential mechanisms, through which insulin resistance and hyperinsulinemia can contribute to renal injury.
代谢综合征的大多数基本组成部分，即2型糖尿病、高血压、肥胖或高密度脂蛋白胆固醇水平低，除了是心血管疾病的主要危险因素外，还与慢性肾脏病风险增加有关。然而，过去几年进行的多项流行病学研究表明，该综合征的核心组成部分胰岛素抵抗以及代偿性高胰岛素血症与慢性肾脏病患病率增加独立相关。此外，基础研究支持存在多种将胰岛素抵抗和高胰岛素血症与肾损伤联系起来的途径。胰岛素本身可促进肾细胞增殖，并刺激其他重要生长因子如胰岛素样生长因子-1和转化生长因子β的产生。胰岛素还上调系膜细胞中血管紧张素II 1型受体的表达，从而增强血管紧张素II在肾脏中的有害作用，并刺激内皮素-1的产生和肾脏作用。此外，胰岛素抵抗和高胰岛素血症与内皮细胞一氧化氮生成减少和氧化应激增加有关，这也与糖尿病肾病的进展有关。本综述分析了上述及其他潜在机制，通过这些机制胰岛素抵抗和高胰岛素血症可导致肾损伤。
