一氧化氮制剂会损害大鼠骨骼肌中胰岛素介导的信号转导。

Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle.

作者信息

Badal Simone, Brown Paul D, Ragoobirsingh Dalip

机构信息

Department of Basic Medical Sciences, Section of Biochemistry, The University of the West Indies, Kingston, Jamaica.

出版信息

BMC Biochem. 2006 May 27;7:17. doi: 10.1186/1471-2091-7-17.

BACKGROUND

Evidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the early events in insulin signaling in rat skeletal myocytes.

RESULTS

Skeletal muscle cells from 6-8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml) in the presence or absence of glucose (25 mM) and insulin (100 nM). Cellular insulin receptor-beta levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO).

CONCLUSION

These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.

背景

有证据表明，外源性给予一氧化氮（NO）可诱导骨骼肌中的胰岛素抵抗。我们研究了两种NO供体，即S-亚硝基-N-乙酰-D，L-青霉胺（SNAP）和S-亚硝基谷胱甘肽（GSNO）对大鼠骨骼肌细胞胰岛素信号传导早期事件的调节作用。

结果

在存在或不存在葡萄糖（25 mM）和胰岛素（100 nM）的情况下，用SNAP或GSNO（25 ng/ml）处理6-8周龄Sprague-Dawley大鼠的骨骼肌细胞。与胰岛素刺激的对照相比，这些细胞中的细胞胰岛素受体β水平和IRS-1中的酪氨酸磷酸化显著降低，而IRS-1中的丝氨酸磷酸化显著增加。使用NO清除剂2-（4-羧基苯基）-4,4,5,5-四甲基咪唑啉-1-氧基3-氧化物（羧基-PTIO）可使水平恢复到接近正常水平。