Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle
Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle
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DOI：
10.2337/diabetes.50.2.241
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发表时间：
2001-02-01
期刊：
影响因子：
7.7
通讯作者：
Goodyear, LJ
中科院分区：
文献类型：
--
作者：
Higaki, Y;Hirshman, MF;Goodyear, LJ
胰岛素、收缩和一氧化氮（NO）供体硝普钠（SNP）都能增加骨骼肌中的葡萄糖转运。一些报告表明，NO是胰岛素和/或收缩刺激的运输的关键介质。为了确定导致NO刺激的葡萄糖摄取的机制是否类似于胰岛素或收缩依赖性信号传导途径，用SNP的各种组合处理来自大鼠的分离的比目鱼肌和趾长伸肌（EDL）。（最大10 mmol/l），胰岛素（最大50 mU/ml），电刺激产生收缩（最多10分钟）、渥曼青霉素（100 nmol/l）和/或NO合酶（NOS）抑制剂N-G-单甲基-L-精氨酸（L-NMMA）（0.1 mmol/l）。SNP+胰岛素和SNP+收缩的组合对2-脱氧葡萄糖摄取都具有完全累加效应。Wortmannin完全抑制胰岛素刺激的葡萄糖转运，仅轻微抑制SNP刺激的2-脱氧葡萄糖摄取，而L-NMMA。不抑制收缩刺激的2-脱氧葡萄糖摄取。SNP显著增加了5'AMP活化蛋白激酶（AMPK）的α 1催化亚基的活性，AMPK是一种参与介导燃料耗尽细胞中葡萄糖转运的信号分子。在大鼠饮水中添加NOS抑制剂N-G-硝基-L-精氨酸甲酯（L-NAME）（1 mg/ml）2天，对运动引起的肌肉2-脱氧葡萄糖摄取增加无影响。这些数据表明，NO刺激葡萄糖摄取的机制，是不同的胰岛素和收缩信号通路。
Insulin, contraction, and the nitric oxide (NO) donor, sodium nitroprusside (SNP), all increase glucose transport in skeletal muscle. Some reports suggest that NO is a critical mediator of insulin- and/or contraction-stimulated transport. To determine if the mechanism leading to NO-stimulated glucose uptake is similar to the insulin- or contraction-dependent signaling pathways, isolated soleus and extensor digitorum longus (EDL) muscles from rats were treated with various combinations of SNP (maximum 10 mmol/l), insulin (maximum 50 mU/ml), electrical stimulation to produce contractions (maximum 10 min), wortmannin (100 nmol/I), and/or the NO synthase (NOS) inhibitor N-G-monomethyl-L-arginine (L-NMMA) (0.1 mmol/l). The combinations of SNP plus insulin and SNP plus contraction both had fully additive effects on 2-deoxyglucose uptake. Wortmannin completely inhibited insulin-stimulated glucose transport and only slightly inhibited SNP-stimulated 2-deoxyglucose uptake, whereas L-NMMA. did not inhibit contraction-stimulated 2-deoxyglucose uptake. SNP significantly increased the activity of the alpha1 catalytic subunit of 5' AMP-activated protein kinase (AMPK), a signaling molecule that has been implicated in mediating glucose transport in fuel-depleted cells. Addition of the NOS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) (1 mg/ml) to the drinking water of rats for 2 days failed to affect the increase in muscle 2-deoxyglucose uptake in response to treadmill exercise. These data suggest that NO stimulates glucose uptake through a mechanism that is distinct from both the insulin and contraction signaling pathways.