Copenhagen Muscle Research Centre, Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.
Diabetes. 2011 Jan;60(1):64-73. doi: 10.2337/db10-0698. Epub 2010 Oct 18.
We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance.
Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg⁻¹ · min⁻¹).
Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men (P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by intralipid.
Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.
我们之前的研究表明，与男性相比， overnight fasted 的女性尽管肌细胞内三酰甘油浓度较高，但胰岛素刺激的全身和腿部葡萄糖摄取量更高。女性的肌肉中与脂质代谢相关的蛋白质的 mRNA 水平也高于男性。因此，我们假设女性不易发生脂质诱导的胰岛素抵抗。
在输注脂肪乳或生理盐水 7 小时期间，我们对 16 名年轻、匹配良好的健康男女进行了全身和腿部葡萄糖摄取的胰岛素敏感性研究。在进行正常血糖高胰岛素钳夹（1.42 mU·kg⁻¹·min⁻¹）之前和期间，我们从肌肉活检中获取了样本。
脂肪乳输注使女性的全身葡萄糖输注率降低了 26%，男性降低了 38%（P < 0.05），而在输注脂肪乳后，女性的胰岛素刺激的腿部葡萄糖摄取量仅减少了 45%，而男性减少了 60%。无论输注脂肪乳与否，女性和男性的肝葡萄糖生成在钳夹期间均相似地降低。脂肪乳并未损害肌肉和皮下脂肪中的胰岛素或 AMPK 信号转导，未导致肌肉脂质中间产物的积累，也未损害肌肉中胰岛素刺激的糖原合酶活性或增加血浆中炎症细胞因子的浓度。在急性暴露于脂肪酸的情况下，离体的巨大肌浆网囊泡中的葡萄糖转运并未减少。脂肪乳输注会增加腿部的乳酸释放并降低呼吸交换率。
与男性相比，脂肪乳输注会导致女性肌肉葡萄糖摄取的胰岛素抵抗程度降低。这种胰岛素抵抗不是由于经典的胰岛素信号转导减少、脂质中间产物积累、炎症或直接抑制 GLUT 活性引起的。相反，脂肪乳输注后腿部乳酸释放增加和葡萄糖氧化减少可能表明葡萄糖代谢存在代谢反馈调节。
