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

被引:31
|
作者
Premilovac, Dino [1 ]
Richards, Stephen M. [2 ]
Rattigan, Stephen [1 ]
Keske, Michelle A. [1 ]
机构
[1] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7000, Australia
[2] Univ Tasmania, Fac Hlth, Sch Med, Hobart, Tas, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
ACE inhibition; High sodium; Insulin resistance; Microvasculature; Quinapril; Skeletal muscle; MUSCLE IN-VIVO; MEDIATED CAPILLARY RECRUITMENT; SALT-SENSITIVE HYPERTENSION; HUMAN FOREARM MUSCLE; DIET-FED RATS; SKELETAL-MUSCLE; GLUCOSE-UPTAKE; MICROVASCULAR RECRUITMENT; ANGIOTENSIN-II; BLOOD-FLOW;
D O I
10.1007/s00125-014-3373-y
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. 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. 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. 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.
引用
收藏
页码:2586 / 2595
页数:10
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