Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling.
Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling.
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作者：
Høeg LD;Sjøberg KA;Jeppesen J;Jensen TE;Frøsig C;Birk JB;Bisiani B;Hiscock N;Pilegaard H;Wojtaszewski JF;Richter EA;Kiens B
我们以前已经证明，尽管肌细胞内三酰甘油浓度高于男性，但整夜禁食的女性具有更高的胰岛素刺激的全身和腿部葡萄糖摄取。女性肌肉中与脂质代谢相关的蛋白质mRNA水平也高于男性。因此，我们假设女性不太容易发生脂质诱导的胰岛素抵抗。对16名健康青年男女进行胰岛素或生理盐水输注7 h后全身及腿部葡萄糖处理的胰岛素敏感性研究。在正常血糖-高胰岛素钳夹（1.42 mU · kg−1 · min−1）之前和期间进行肌肉活检。输注胰岛素后，女性全身葡萄糖输注率降低了26%，男性降低了38%（P < 0.05），胰岛素刺激的腿部葡萄糖摄取在女性（45%）输注胰岛素后显著低于男性（60%）。在钳夹期间，无论是否输注胰岛素，女性和男性的肝脏葡萄糖生成均减少。胰岛素样肽不损害肌肉和皮下脂肪中的胰岛素或AMPK信号传导，不引起肌肉脂质中间体的积累，不损害肌肉中胰岛素刺激的糖原合成酶活性或增加炎性细胞因子的血浆浓度。在巨大的肌膜囊泡的体外葡萄糖转运没有减少急性暴露于脂肪酸。肌内营养素可增加下肢乳酸释放，降低呼吸交换率。胰岛素输注导致女性肌肉葡萄糖摄取的胰岛素抵抗比男性少。这种胰岛素抵抗不是由于经典胰岛素信号传导减少、脂质中间体积累、炎症或GLUT活性的直接抑制。相反，用胰岛素输注的较高腿部乳酸盐释放和较低葡萄糖氧化可能表明葡萄糖代谢的代谢反馈调节。
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.
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DOI：
10.1152/ajpendo.00133.2007
发表时间：
2007-11-01
影响因子：
5.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Olefsky, JM
影响因子：
5.5
作者：
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通讯作者：
Kiens, Bente
DOI：
10.1152/ajpendo.00316.2005
发表时间：
2006-03-01
影响因子：
5.1
作者：
Kraegen, EW;Saha, AK;Ruderman, NB
通讯作者：
Ruderman, NB
DOI：
10.1042/bj20082055
发表时间：
2009-03-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Richter EA;Ruderman NB
通讯作者：
Ruderman NB