Acute and chronic exposure to tumor necrosis factor-alpha fails to affect insulin-stimulated glucose metabolism of isolated rat soleus muscle.
To better understand the effects of tumor necrosis factor-alpha (TNF alpha) on insulin sensitivity, direct interaction of the peptide with freshly isolated rat soleus muscle strips was investigated. Muscles were exposed to TNF alpha at concentrations ranging from 0.01-5 nmol/liter. Rates of insulin-stimulated (5 or 100 nmol/liter) glucose metabolism were determined after periods of TNF alpha preexposure of 30 min, 6 h, and 24 h. Independent of exposure time, TNF alpha failed to exert any significant effect on rates of 3H-2-deoxy-glucose transport (stimulation by 100 nmol/liter insulin after preincubation without vs. with 5 nmol/liter TNF alpha, cpm/mg x h: 30 min, 779 +/- 29 vs. 725 +/- 29; 6 h, 652 +/- 56 vs. 617 +/- 60; 24 h, 911 +/- 47 vs. 936 +/- 31) or glucose incorporation into glycogen (micromol/g x h: 30 min, 5.19 +/- 0.22 vs. 5.25 +/- 0.41; 6 h, 2.08 +/- 0.10 vs. 2.09 +/- 0.17; 24 h, 2.51 +/- 0.21 vs. 2.41 +/- 0.26). In parallel, TNF alpha neither affected insulin-stimulated rates of glucose oxidation (CO2 production) and anaerobic glycolysis (lactate release), nor muscle glycogen content. In conclusion, these findings do not support the hypothesis of muscle insulin desensitization by TNF alpha via autocrine or paracrine mechanisms. The obtained data favor the concept that TNF alpha-dependent muscle insulin resistance in vivo depends on indirect effects rather than direct interaction of the peptide with skeletal muscle.
Fürnsinn
C
C
Department of Medicine III, University of Vienna, Austria. clemens.fuernsinn@akh-wien.ac.at
Neschen
S
S
Wagner
O
O
Roden
M
M
Bisschop
M
M
Waldhäusl
W
W
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose