Kolka Cathryn M, Richey Joyce M, Castro Ana Valeria B, Broussard Josiane L, Ionut Viorica, Bergman Richard N
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
Am J Physiol Endocrinol Metab. 2015 Jun 1;308(11):E1001-9. doi: 10.1152/ajpendo.00015.2015. Epub 2015 Apr 7.
Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance.
血浆游离脂肪酸（FFA）水平升高会导致骨骼肌出现胰岛素抵抗。此前，我们已经表明，脂质输注诱导的实验性胰岛素抵抗会阻止胰岛素在肌肉中扩散，并且我们推测这会导致胰岛素从血浆转移至肌肉间质的过程受损。因此，我们向麻醉的犬模型中输注脂质，并在高胰岛素正常血糖钳夹条件下，测量胰岛素在淋巴中的出现情况，以此作为一种采样肌肉间质的方法。尽管脂质输注降低了葡萄糖输注速率，并诱导了外周和肝脏胰岛素抵抗，但我们未能检测到胰岛素进入淋巴的过程受损。有趣的是，尽管血浆FFA显著增加了10倍，但脂质输注后，我们在淋巴中几乎未检测到游离脂肪酸或甘油三酯的增加。因此，我们得出结论，在钳夹条件下，脂质输注诱导的实验性胰岛素抵抗不会减少胰岛素进入骨骼肌的机会。这表明在该模型中，外周胰岛素抵抗可能是由于细胞对胰岛素的敏感性降低所致，然而我们并未检测到可能导致细胞胰岛素抵抗的组织微环境变化。
