在大鼠离体骨骼肌中,一氧化氮合酶抑制不能阻止5′-氨基咪唑-4-羧酰胺-核糖核苷活化的葡萄糖运输。

IF 2.4 4区 医学 Q3 PHARMACOLOGY & PHARMACY
T J Stephens, B J Canny, R J Snow, G K McConell
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引用次数: 34

摘要

1. 核苷中间体5′-氨基咪唑-4-羧酰胺核糖核苷(AICAR)激活骨骼肌amp活化蛋白激酶(AMPK)并增加葡萄糖摄取。AMPK磷酸化骨骼肌纤维中的神经元一氧化氮合酶(nNOS)mu。有证据表明AMPK和nNOSmu都可能参与收缩刺激葡萄糖摄取的调节。2. 我们检测了大鼠骨骼肌中AICAR和收缩刺激的葡萄糖摄取是否由NOS介导。3.将离体大鼠耳蜗上膜肌肉进行体外电刺激收缩10分钟和/或在AICAR (2 mmol/L)或NOS抑制剂ng - monom甲基-L-精氨酸(L- nmma)存在或不存在的情况下孵育;100 micromol / L)。4. 肌肉收缩显著(P < 0.05)改变了肌肉代谢谱。相比之下,AICAR和L-NMMA对肌肉代谢谱没有影响,但AICAR增加了肌肉5′-氨基咪唑-4-羧酰胺核糖核苷酸(ZMP)和AICAR含量。一氧化氮合酶抑制导致基础3- o -甲基葡萄糖转运减少(P < 0.05),这在所有处理中都有观察到。5′-氨基咪唑-4-羧酰胺核糖核苷显著增加(P < 0.05)基础以上葡萄糖转运,NOS抑制使其略有下降(NOS抑制使基础以上葡萄糖转运增加209%,而NOS抑制使基础以上葡萄糖转运增加184%)。收缩显著增加葡萄糖在基础以上的转运,NOS抑制显著降低葡萄糖转运(增加107% vs增加31%)。5′-氨基咪唑-4-羧酰胺-核糖核苷加收缩剂联合使用对葡萄糖转运无附加作用。5. 这些结果表明NO在基础葡萄糖摄取中起作用,并可能调节收缩刺激的葡萄糖摄取。然而,NOS/一氧化氮似乎不是aicar刺激骨骼肌葡萄糖摄取的信号中间体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
5'-aminoimidazole-4-carboxyamide-ribonucleoside-activated glucose transport is not prevented by nitric oxide synthase inhibition in rat isolated skeletal muscle.

1. The nucleoside intermediate 5'-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) activates skeletal muscle AMP-activated protein kinase (AMPK) and increases glucose uptake. The AMPK phosphorylates neuronal nitric oxide synthase (nNOS)mu in skeletal muscle fibres. There is evidence that both AMPK and nNOSmu may be involved in the regulation of contraction-stimulated glucose uptake. 2. We examined whether both AICAR- and contraction-stimulated glucose uptake were mediated by NOS in rat skeletal muscle. 3. Rat isolated epitrochlearis muscles were subjected in vitro to electrically stimulated contractions for 10 min and/or incubated in the presence or absence of AICAR (2 mmol/L) or the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; 100 micromol/L). 4. Muscle contraction significantly (P < 0.05) altered the metabolic profile of the muscle. In contrast, AICAR and L-NMMA had no effect on the metabolic profile of the muscle, except that AICAR increased muscle 5'-aminoimidazole-4-carboxyamide-ribonucleotide (ZMP) and AICAR content. Nitric oxide synthase inhibition caused a small but significant (P < 0.05) reduction in basal 3-O-methylglucose transport, which was observed in all treatments. 5'-Aminoimidazole-4-carboxyamide-ribonucleoside significantly increased (P < 0.05) glucose transport above basal, with NOS inhibition decreasing this slightly (increased by 209% above basal compared with 184% above basal with NOS inhibition). Contraction significantly increased glucose transport above basal, with NOS inhibition substantially reducing this (107% increase vs 31% increase). 5'-Aminoimidazole-4-carboxyamide-ribonucleoside plus contraction in combination were not additive on glucose transport. 5. These results suggest that NO plays a role in basal glucose uptake and may regulate contraction-stimulated glucose uptake. However, NOS/nitric oxide do not appear to be signalling intermediates in AICAR-stimulated skeletal muscle glucose uptake.

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来源期刊
Clinical and Experimental Pharmacology and Physiology
Clinical and Experimental Pharmacology and Physiology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
自引率
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128
期刊介绍: Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.
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