Dataset Information

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

ABSTRACT:

Background

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.

Methods

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.

Findings

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.

Interpretation

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 ?-and-?-adrenergic receptors to reduce IR in patients with CKD. FUND: National Natural Science Foundation of China.

SUBMITTER: Cao W

PROVIDER: S-EPMC6286258 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Cao Wei W Shi Meng M Wu Liling L Yang Zhichen Z Yang Xiaobing X Liu Hongfa H Xu Xin X Liu Youhua Y Wilcox Christopher S CS Hou Fan Fan FF

EBioMedicine 20181111

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>High-salt in 5/6-nephrectom ...[more]

PMID: 30429087

Similar Datasets

Project description:BackgroundCorrection of metabolic acidosis (MA) with nutritional therapy or bicarbonate administration is widely used in chronic kidney disease (CKD) patients. However, it is unknown whether these interventions reduce insulin resistance (IR) in diabetic patients with CKD. We sought to evaluate the effect of MA correction on endogenous insulin action in diabetic type 2 (DM2) CKD patients.MethodsA total of 145 CKD subjects (83 men e 62 women) with DM2 treated with oral antidiabetic drugs were included in the study and followed up to 1 year. All patients were randomly assigned 1:1 to either open-label (A) oral bicarbonate to achieve serum bicarbonate levels of 24-28 mmol/L (treatment group) or (B) no treatment (control group). The Homeostatic model assessment (HOMA) index was used to evaluate IR at study inception and conclusion. Parametric and non-parametric tests as well as linear regression were used.ResultsAt baseline no differences in demographic and clinical characteristics between the two groups was observed. Average dose of bicarbonate in the treatment group was 0.7 ± 0.2 mmol/kg. Treated patients showed a better metabolic control as confirmed by lower insulin levels (13.4 ± 5.2 vs 19.9 ± 6.3; for treated and control subjects respectively; p < 0.001), Homa-IR (5.9[5.0-7.0] vs 6.3[5.3-8.2]; p = 0.01) and need for oral antidiabetic drugs. The serum bicarbonate and HOMA-IR relationship was non-linear and the largest HOMA-IR reduction was noted for serum bicarbonate levels between 24 and 28 mmol/l. Adjustment for confounders, suggests that serum bicarbonate rather than treatment drives the effect on HOMA-IR.ConclusionsSerum bicarbonate is related to IR and the largest HOMA-IR reduction is noted for serum bicarbonate between 24 and 28 mmol/l. Treatment with bicarbonate influences IR. However, changes in serum bicarbonate explains the effect of treatment on HOMA index. Future efforts are required to validate these results in diabetic and non-diabetic CKD patients.Trial registrationThe trial was registered at www.clinicaltrial.gov (Use of Bicarbonate in Chronic Renal Insufficiency (UBI) study - NCT01640119 ).

Dataset Information

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

Background

Methods

Findings

Interpretation

Publications

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

Similar Datasets

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