The contribution of skeletal muscle tumor necrosis factor-α to insulin resistance and hypertension in fructose-fed rats

被引:86
作者
Togashi, N [1 ]
Ura, N [1 ]
Higashiura, K [1 ]
Murakami, H [1 ]
Shimamoto, K [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
关键词
tumor necrosis factor-alpha; insulin resistance; fructose-fed rat; angiotensin II; hypertension;
D O I
10.1097/00004872-200018110-00011
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objective The aim of this study was to determine the role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle tissue in insulin resistance and hypertension and the effect of anti-hypertensive medicine on skeletal muscle TNF-alpha in fructose-induced insulin-resistant and hypertensive rats (fructose-fed rats: FFR). Design and methods Six-week-old male Sprague-Dawley rats were fed either normal rat chow or fructose-rich chow. For the last 2 weeks of a 6-week period of either diet, the rats were treated with a vehicle (control or FFR); temocapril, an angiotensin converting enzyme inhibitor (ACEI); or CS-866, an angiotensin II type 1 receptor blocker (ARB). The euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity (M value), TNF-alpha levels in soleus and extensor digitorum longus (EDL) muscles and epididymal fat pads were measured. We also measured the TNF-alpha concentration in an incubated medium secreted from soleus muscle strips with or without angiotensin II. Results TNF-alpha levels were significantly higher in the soleus and EDL muscles, but not in the epididymal fat, in the FFRs compared with the control rats. Temocapril and CS-866 lowered systolic blood pressure, improved insulin resistance, and reduced TNF-alpha in both skeletal muscles. There were significant negative correlations between M values and TNF-alpha levels in both soleus and EDL muscles, Also, the soleus muscle strip incubation with 10(-7) mol/l angiotensin II increased TNF-alpha secreted into the incubation medium compared to the incubation without angiotensin II. These results suggest that skeletal muscle TNF-alpha is linked to insulin resistance and hypertension and that angiotensin II may be one of the factors that regulate skeletal muscle TNF-alpha. J Hypertens 18:1605-1610 (C) 2000 Lippincott Williams & Wilkins.
引用
收藏
页码:1605 / 1610
页数:6
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