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A vascular mechanism for high-sodium-induced insulin resistance in rats


Premilovac, D and Richards, SM and Rattigan, S and Keske, MA, A vascular mechanism for high-sodium-induced insulin resistance in rats, Diabetologia: Clinical and Experimental Diabetes and Metabolism, 57, (12) pp. 2586-2595. ISSN 0012-186X (2014) [Refereed Article]

Copyright Statement

Copyright 2014 Springer

DOI: doi:10.1007/s00125-014-3373-y


AIMS/HYPOTHESIS: High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor linking HS intake to insulin resistance. METHODS: Sprague Dawley rats were fed a control (0.31% wt/wt NaCl) or HS (8.00% wt/wt NaCl) diet for 4 weeks and subjected to euglycaemic-hyperinsulinaemic clamp (10 mU min-1 kg-1) or constant-flow pump-perfused hindlimb studies following an overnight fast. A separate group of HS rats was given quinapril during the dietary intervention and subjected to euglycaemic-hyperinsulinaemic clamp as above. RESULTS: HS intake had no effect on body weight or fat mass or on fasting glucose, insulin, endothelin-1 or NEFA concentrations. However, HS impaired whole body and skeletal muscle glucose uptake, in addition to a loss of insulin-stimulated microvascular recruitment. These effects were present despite enhanced insulin signalling (Akt) in both liver and skeletal muscle. Constant-flow pump-perfused hindlimb experiments revealed normal insulin-stimulated myocyte glucose uptake in HS-fed rats. Quinapril treatment restored insulin-mediated microvascular recruitment and muscle glucose uptake in vivo. CONCLUSIONS/INTERPRETATION: HS-induced insulin resistance is driven by impaired microvascular responsiveness to insulin, and is not due to metabolic or signalling defects within myocytes or liver. These results imply that reducing sodium intake may be important not only for management of hypertension but also for insulin resistance, and highlight the vasculature as a potential therapeutic target in the prevention of insulin resistance.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Endocrinology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Premilovac, D (Dr Dino Premilovac)
UTAS Author:Richards, SM (Dr Stephen Richards)
UTAS Author:Rattigan, S (Professor Stephen Rattigan)
UTAS Author:Keske, MA (Dr Michelle Keske)
ID Code:96415
Year Published:2014
Web of Science® Times Cited:22
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-11-04
Last Modified:2017-11-02

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