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

Premilovac, Dino, Richards, Stephen M., Rattigan, Stephen and Keske, Michelle A. 2014, A vascular mechanism for high-sodium-induced insulin resistance in rats, Diabetologia, vol. 57, no. 12, pp. 2586-2595, doi: 10.1007/s00125-014-3373-y.

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Title A vascular mechanism for high-sodium-induced insulin resistance in rats
Author(s) Premilovac, Dino
Richards, Stephen M.
Rattigan, Stephen
Keske, Michelle A.ORCID iD for Keske, Michelle A. orcid.org/0000-0003-4214-7628
Journal name Diabetologia
Volume number 57
Issue number 12
Start page 2586
End page 2595
Total pages 10
Publisher Springer Verlag
Place of publication Berlin, Germany
Publication date 2014-12
ISSN 1432-0428
Keyword(s) Animals
Blood Glucose
Endothelin-1
Fatty Acids, Nonesterified
Glucose Clamp Technique
Insulin
Insulin Resistance
Liver
Male
Muscle, Skeletal
Rats
Rats, Sprague-Dawley
Sodium Chloride, Dietary
Tetrahydroisoquinolines
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
ACE inhibition
High sodium
Microvasculature
Quinapril
Skeletal muscle
Summary 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.
Language eng
DOI 10.1007/s00125-014-3373-y
Field of Research 110201 Cardiology (incl Cardiovascular Diseases)
110306 Endocrinology
111103 Nutritional Physiology
1103 Clinical Sciences
1114 Paediatrics And Reproductive Medicine
1117 Public Health And Health Services
Socio Economic Objective 920104 Diabetes
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Springer-Verlag Berlin Heidelberg
Persistent URL http://hdl.handle.net/10536/DRO/DU:30092196

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