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


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.
Togashi
N
N
2nd Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan. ntogashi@sapmed.ac.jp
Ura
N
N
Higashiura
K
K
Murakami
H
H
Shimamoto
K
K
D000273:Adipose Tissue / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D004822:Epididymis / Q000378:metabolism; D005632:Fructose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D000068557:Olmesartan Medoxomil; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007093:Imidazoles; D013777:Tetrazoles; D013841:Thiazepines; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D000068557:Olmesartan Medoxomil; C055603:temocapril hydrochloride