Zha Dongqing, Wu Xiaoyan, Gao Ping
Division of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
Endocrinology. 2017 Jul 1;158(7):2022-2034. doi: 10.1210/en.2016-1765.
Diabetic kidney disease (DKD) is a major complication for diabetic patients. Adiponectin is an insulin sensitizer and anti-inflammatory adipokine and is mainly secreted by adipocytes. Two types of adiponectin receptors, AdipoR1 and AdipoR2, have been identified. In both type 1 and type 2 diabetes (T2D) patients with DKD, elevated adiponectin serum levels have been observed, and adiponectin serum level is a prognostic factor of end-stage renal disease. Renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in diabetic nephropathy by either increasing biodegradation or elimination of adiponectin in the kidneys, or enhancing production of adiponectin in adipose tissue. Increases in adiponectin levels resulted in amelioration of albuminuria, glomerular hypertrophy, and reduction of inflammatory response in kidney tissue. The renoprotection of adiponectin is associated with improvement of the endothelial dysfunction, reduction of oxidative stress, and upregulation of endothelial nitric oxide synthase expression through activation of adenosine 5'-monophosphate-activated protein kinase by AdipoR1 and activation of peroxisome proliferator-activated receptor (PPAR)-α signaling pathway by AdipoR2. Several single nucleotide polymorphisms in the AdipoQ gene, including the promoter, are associated with increased risk of the development of T2D and DKD. Renin-angiotensin-aldosterone system blockers, adiponectin receptor agonists, and PPAR agonists (e.g., tesaglitazar, thiazolidinediones, fenofibrate), which increase plasma adiponectin levels and adiponectin receptors expression, may be potential therapeutic drugs for the treatment of DKD.
糖尿病肾病（DKD）是糖尿病患者的主要并发症。脂联素是一种胰岛素增敏剂和抗炎脂肪因子，主要由脂肪细胞分泌。已鉴定出两种类型的脂联素受体，即脂联素受体1（AdipoR1）和脂联素受体2（AdipoR2）。在1型糖尿病和2型糖尿病（T2D）合并DKD的患者中，均观察到血清脂联素水平升高，且血清脂联素水平是终末期肾病的一个预后因素。肾功能不全和肾小管损伤可能通过增加肾脏中脂联素的生物降解或清除，或增强脂肪组织中脂联素的产生，在糖尿病肾病患者血清和尿液脂联素水平升高中起作用。脂联素水平升高可改善蛋白尿、肾小球肥大，并减轻肾组织中的炎症反应。脂联素的肾脏保护作用与内皮功能障碍的改善、氧化应激的减轻以及通过AdipoR1激活腺苷5'-单磷酸激活蛋白激酶和通过AdipoR2激活过氧化物酶体增殖物激活受体（PPAR）-α信号通路来上调内皮型一氧化氮合酶表达有关。脂联素基因（AdipoQ）中的几个单核苷酸多态性，包括启动子，与T2D和DKD发生风险增加有关。肾素-血管紧张素-醛固酮系统阻滞剂、脂联素受体激动剂和PPAR激动剂（如替格列扎、噻唑烷二酮类、非诺贝特）可增加血浆脂联素水平和脂联素受体表达，可能是治疗DKD的潜在治疗药物。
