Fürnsinn C, Neschen S, Wagner O, Roden M, Bisschop M, Waldhäusl W
Department of Medicine III, University of Vienna, Austria.
Endocrinology. 1997 Jul;138(7):2674-9. doi: 10.1210/endo.138.7.5219.
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.
为了更好地理解肿瘤坏死因子-α（TNFα）对胰岛素敏感性的影响，研究了该肽与新鲜分离的大鼠比目鱼肌条的直接相互作用。将肌肉暴露于浓度范围为0.01 - 5 nmol/升的TNFα中。在TNFα预暴露30分钟、6小时和24小时后，测定胰岛素刺激（5或100 nmol/升）的葡萄糖代谢速率。与暴露时间无关，TNFα对3H-2-脱氧葡萄糖转运速率（预孵育无5 nmol/升TNFα与有5 nmol/升TNFα后用100 nmol/升胰岛素刺激，cpm/mg×小时：30分钟，779±29对725±29；6小时，652±56对617±60；24小时，911±47对936±31）或葡萄糖掺入糖原（微摩尔/克×小时：30分钟，5.19±0.22对5.25±0.41；6小时，2.08±0.10对2.09±0.17；24小时，2.51±0.21对2.41±0.26）均未产生任何显著影响。同时，TNFα既不影响胰岛素刺激的葡萄糖氧化（二氧化碳产生）和无氧糖酵解（乳酸释放）速率，也不影响肌肉糖原含量。总之，这些发现不支持TNFα通过自分泌或旁分泌机制使肌肉胰岛素脱敏的假说。所获得的数据支持这样一种观点，即体内TNFα依赖性肌肉胰岛素抵抗取决于间接作用，而非该肽与骨骼肌的直接相互作用。
