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

Abstract

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.

• Authors: N Togashi, N Ura, K Higashiura, H Murakami, K Shimamoto
• Journal: Journal of hypertension (J Hypertens) Vol. 18 Issue 11 Pg. 1605-10 (Nov 2000) ISSN: 0263-6352 [Print] England
• PMID: 11081773 (Publication Type: Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Blood Glucose
• Imidazoles
• Tetrazoles
• Thiazepines
• Tumor Necrosis Factor-alpha
• Fructose
• Olmesartan Medoxomil
• temocapril hydrochloride

Topics

• Adipose Tissue (metabolism)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Blood Glucose
• Blood Pressure (drug effects, physiology)
• Body Weight
• Epididymis (metabolism)
• Fructose (pharmacology)
• Glucose Clamp Technique
• Heart Rate (drug effects, physiology)
• Hypertension (metabolism)
• Imidazoles (pharmacology)
• Insulin Resistance (physiology)
• Male
• Muscle, Skeletal (metabolism)
• Olmesartan Medoxomil
• Rats
• Rats, Sprague-Dawley
• Tetrazoles (pharmacology)
• Thiazepines (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)