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EBioMedicine. 2018 Nov;37:281-293. doi: 10.1016/j.ebiom.2018.10.054. Epub 2018 Nov 11.

A renal-cerebral-peripheral sympathetic reflex mediates insulin resistance in chronic kidney disease.

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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. Electronic address:
Division of Nephrology, Nanfang Hospital, 1838 North Guangzhou Avenue, Guangzhou 510515, PR China.. Electronic address:



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.


Adipose tissue; Chronic kidney disease; Insulin resistance; Renin-angiotensin system; Salt; Sympathetic reflex

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