Division of Nephrology, Nanfang Hospital, 1838 North Guangzhou Avenue, Guangzhou 510515, PR China.
Division of Nephrology and Hypertension, Georgetown University Medical Central, 3800 Reservoir Road, NW, 6 PHC Bldg, F6003, Washington, DC 20007, USA.
EBioMedicine. 2018 Nov;37:281-293. doi: 10.1016/j.ebiom.2018.10.054. Epub 2018 Nov 11.
Insulin resistance (IR) complicates chronic kidney disease (CKD). We tested the hypothesis that CKD activates a broad reflex response from the kidneys and the white adipose tissue to impair peripheral glucose uptake and investigated the role of salt intake in this process.
5/6-nephrectomized rats were administered normal- or high-salt for 3 weeks. Conclusions were tested in 100 non-diabetic patients with stage 3-5 CKD.
High-salt in 5/6-nephrectomized rats decreased insulin-stimulated 2-deoxyglucose uptake >25% via a sympathetic nervous system (SNS) reflex that linked the IR to reactive oxygen species (ROS) and the renin-angiotensin system (RAS) in brain and peripheral tissues. Salt-loading in CKD enhanced inflammation in adipose tissue and skeletal muscle, and enhanced the impairment of insulin signaling and Glut4 trafficking. Denervation of the kidneys or adipose tissue or deafferentation of adipose tissue improved IR >40%. In patients with non-diabetic CKD, IR was positively correlated with salt intake after controlling for cofounders (r = 0.334, P = 0.001) and was linked to activation of the RAS/SNS and to impaired glucose uptake in adipose tissue and skeletal muscle, all of which depended on salt intake.
CKD engages a renal/adipose-cerebral-peripheral sympathetic reflex that activates the RAS/ROS axes to promote IR via local inflammation and impaired Glut4 trafficking that are enhanced by high-salt intake. The findings point to a role for blockade of RAS or α-and-β-adrenergic receptors to reduce IR in patients with CKD. FUND: National Natural Science Foundation of China.
胰岛素抵抗（IR）使慢性肾脏病（CKD）复杂化。我们检验了这样一个假设，即 CKD 会激活肾脏和白色脂肪组织的广泛反射反应，从而损害外周葡萄糖摄取，并研究了盐摄入量在这一过程中的作用。
对 5/6 肾切除大鼠给予正常或高盐饮食 3 周。在 100 名非糖尿病、3-5 期 CKD 患者中检验了这些结论。
在 5/6 肾切除大鼠中，高盐通过一种交感神经系统（SNS）反射使胰岛素刺激的 2-脱氧葡萄糖摄取减少了>25%，这种反射将 IR 与大脑和外周组织中的活性氧（ROS）和肾素-血管紧张素系统（RAS）联系起来。在 CKD 中，盐负荷增强了脂肪组织和骨骼肌中的炎症，并增强了胰岛素信号和 Glut4 易位的损害。肾脏或脂肪组织去神经支配或脂肪组织去传入神经支配可使 IR 改善>40%。在非糖尿病 CKD 患者中，IR 与盐摄入量呈正相关，在控制混杂因素后（r=0.334，P=0.001），并且与 RAS/SNS 的激活以及脂肪组织和骨骼肌葡萄糖摄取受损有关，所有这些都依赖于盐摄入量。
CKD 会引发肾脏/脂肪-大脑-外周性交感反射，通过局部炎症和 Glut4 易位受损来激活 RAS/ROS 轴，促进 IR，而高盐摄入会增强这些作用。这些发现表明，在 CKD 患者中，阻断 RAS 或α-和β-肾上腺素受体可能会降低 IR。
国家自然科学基金。
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