AICAR and hyperosmotic stress increase insulin-stimulated glucose transport.

AICAR and hyperosmotic stress increase insulin-stimulated glucose transport.
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AICAR 和高渗应激会增加胰岛素刺激的葡萄糖转运。

DOI:
10.1152/japplphysiol.01297.2004
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发表时间:
2005
期刊:
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子:
--
通讯作者:
Fisher,JonathanS
Fisher,JonathanS
中科院分区:
--
文献类型:
--
作者:
Smith,JillL;Patil,PankajB;Fisher,JonathanS

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葡萄糖转运对胰岛素刺激的敏感性已被证明与骨骼肌中AMP活化蛋白激酶(AMPK)的活化同时发生,表明AMPK在调节胰岛素作用中的作用。本研究的目的是评估AMPK在增强肌细胞胰岛素作用中的可能作用。实验模型涉及胰岛素反应性C2 C12肌管,其在胰岛素存在下显示葡萄糖转运增加两倍。用AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-d-呋喃核糖苷(AICAR)处理肌管,然后恢复2小时,增强了胰岛素刺激葡萄糖转运的能力。同样,在高渗介质中孵育,另一种AMPK激活治疗,与胰岛素协同作用,刺激葡萄糖转运。此外,通过在高渗介质中包含化合物C(AMPK抑制剂)来防止由高渗应激引起的胰岛素作用的增加。此外,iodotubercidin,一种对AMPK有效的一般激酶抑制剂,也阻止了胰岛素和高渗应激对葡萄糖转运的联合作用。这些数据提供的新信息是,以前报道的AICAR对胰岛素作用的影响可推广到肌管,高渗应激和胰岛素协同增加葡萄糖转运,AMPK似乎介导胰岛素作用的增强。
Sensitivity of glucose transport to stimulation by insulin has been shown to occur concomitant with activation of the AMP-activated protein kinase (AMPK) in skeletal muscle, suggesting a role of AMPK in regulation of insulin action. The purpose of the present study was to evaluate a possible role of AMPK in potentiation of insulin action in muscle cells. The experimental model involved insulin-responsive C2C12myotubes that exhibit a twofold increase in glucose transport in the presence of insulin. Treatment of myotubes with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), followed by a 2-h recovery, augmented the ability of insulin to stimulate glucose transport. Similarly, incubation in hyperosmotic medium, another AMPK-activating treatment, acted synergistically with insulin to stimulate glucose transport. Furthermore, the increase in insulin action caused by hyperosmotic stress was prevented by inclusion of compound C, an AMPK inhibitor, in hyperosmotic medium. In addition, iodotubercidin, a general kinase inhibitor that is effective against AMPK, also prevented the combined effects of insulin and hyperosmotic stress on glucose transport. The new information provided by these data is that previously reported AICAR effects on insulin action are generalizable to myotubes, hyperosmotic stress and insulin synergistically increase glucose transport, and AMPK appears to mediate potentiation of insulin action.
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