Laville M, Rigalleau V, Riou J P, Beylot M
INSERM U197 Lyon, France.
Metabolism. 1995 May;44(5):639-44. doi: 10.1016/0026-0495(95)90122-1.
To investigate the respective role of nonesterified fatty acids (NEFA) oxidation and total lipid oxidation in lipid-induced insulin resistance, we measured the response of glucose metabolism to insulin in normal subjects without (control study) or with either heparin (heparin study) or triglycerides (TG) emulsion (Ivelip study) infusion. Three-step euglycemic-mild-hyperinsulinemic clamp studies were performed. Lipid and glucose metabolism were studied using indirect calorimetry and [6,6-2H2]glucose and [1-13C]palmitate infusions. NEFA concentration and turnover and oxidation rates were decreased by insulin in the control study, but were maintained during the heparin and Ivelip infusion studies. Total lipid oxidation was decreased similarly in the control and heparin studies, but was increased during the Ivelip infusion. Stimulation of glucose oxidation and utilization by insulin was reduced in the Ivelip study, but not in the heparin study. Thus, peripheral insulin resistance was observed in the presence of a combined increase in total lipid and NEFA oxidation, but not during an isolated increase in NEFA oxidation. On the other hand, insulin-induced inhibition of glucose production was impaired in both the heparin and Ivelip studies. We conclude that total lipid oxidation is a major determinant of peripheral insulin resistance, whereas hepatic insulin resistance could be induced even by a moderate increase in NEFA availability.
为了研究非酯化脂肪酸（NEFA）氧化和总脂质氧化在脂质诱导的胰岛素抵抗中的各自作用，我们测量了正常受试者在无（对照研究）或有肝素（肝素研究）或甘油三酯（TG）乳剂（Ivelip研究）输注情况下葡萄糖代谢对胰岛素的反应。进行了三步正常血糖-轻度高胰岛素钳夹研究。使用间接量热法以及输注[6,6-2H2]葡萄糖和[1-13C]棕榈酸酯来研究脂质和葡萄糖代谢。在对照研究中，胰岛素降低了NEFA浓度、周转率和氧化率，但在肝素和Ivelip输注研究期间这些指标保持不变。在对照和肝素研究中，总脂质氧化同样降低，但在Ivelip输注期间增加。在Ivelip研究中，胰岛素对葡萄糖氧化和利用的刺激作用降低，但在肝素研究中未降低。因此，在总脂质和NEFA氧化共同增加时观察到外周胰岛素抵抗，而在NEFA氧化单独增加时未观察到。另一方面，在肝素和Ivelip研究中，胰岛素诱导的葡萄糖生成抑制均受损。我们得出结论，总脂质氧化是外周胰岛素抵抗的主要决定因素，而即使NEFA可用性适度增加也可能诱导肝脏胰岛素抵抗。
