INSULIN EFFECTS ON INTRAMUSCULAR FATTY ACID METABOLISM

肌肉注射TFGA在胰岛素抵抗、肥胖的人中比瘦削、胰岛素敏感的人高2-4倍。这些扩大的脂肪储备被认为是通过葡萄糖脂肪酸循环导致骨骼肌胰岛素抵抗的。然而，耐力训练的人也增加了肌肉中的TGFA，而且不是胰岛素抵抗。如果肌肉内FA与胰岛素抵抗有关，在这两组中，肌肉内TGFA动力学的调节方式必须完全不同。这种差异可能出现在基础条件下对胰岛素的反应，或者两者兼而有之。我们预计内脏肥胖症患者的基础肌肉内TGFA水解率将与增加的TGFA储存量成比例地增加，在这一组中，水解率不会被胰岛素抑制。这一结果将提供有关人类肌肉内FA动力学的第一个可用信息，并将帮助我们理解这种小但潜在重要的脂类在胰岛素抵抗/内脏肥胖综合征中的作用。对最初几项研究获得的样本进行的早期分析显示，肌肉活组织样本中的稳定同位素掺入不足。因此，对方案进行了修改，增加了稳定脂肪酸的剂量，并增加了相同脂肪酸的放射性同位素。为了抵消辐射暴露增加的影响，~3H-葡萄糖被改为稳定的2H-葡萄糖(IRB和辐射安全认证分别为10/2和9/29)。

Intramuscular TFGA are 2-4 fold greater in insulin resistant, obese than in lean, insulin sensitive humans. These enlarged lipid stores are proposed to contribute to skeletal muscle insulin resistance vi the glucose fatty acid cycle. Endurance trained humans also have increased intramuscular TGFA, however, and are not insulin resistant. If intramusclar FA contibute to insulin resistance, intramuscular TGFA kinetics must be regulated quite differently in these two groups. The differences could be present under basal conditions in response to insulin or both. We anticipate that basal intramuscular TGFA hydrolysis will be increased in visceral obesity in proportion to the increased TGFA stores, and that hydrolysis rates will not be inhibited by insulin in this group. The results will provide the first available information regarding the kinetics of intramuscular FA in humans and will help us to understand the role of this small, but potentially important lipid pool in the syndrome of insulin resistance/visceral obesity. Early analysis of samples obtained from the first few studies revealed inadequate stable isotope incorporation into the muscle biopsy specimens. Therefore, a protocol change was made increasing the doses of the stable fatty acids and adding radioisotopes of the same fatty acids. To offset the increase in radiation exposure, the 3H-glucose was changed to stable 2H-glucose (IRB and radiation safety approval 10/2 and 9/29 respectively).