Impaired insulin-stimulated glucose transport in ATM-deficient mouse skeletal muscle.
Impaired insulin-stimulated glucose transport in ATM-deficient mouse skeletal muscle.
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DOI：
10.1139/apnm-2012-0175
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Fisher JS
中科院分区：
文献类型：
--
作者：
Ching JK;Spears LD;Armon JL;Renth AL;Andrisse S;Collins RL 4th;Fisher JS
有报道称，共济失调毛细血管扩张突变（ATM）在胰岛素刺激的Akt磷酸化中起作用，尽管在某些细胞类型中并非如此。由于Akt在导致骨骼肌中葡萄糖转运的胰岛素信号传导中发挥关键作用，骨骼肌是胰岛素刺激下葡萄糖处理的主要组织，因此我们研究了与野生型小鼠相比，缺乏功能ATM的小鼠骨骼肌中胰岛素刺激的Akt磷酸化和/或葡萄糖转运是否会减少。我们发现体外胰岛素刺激的Akt磷酸化在具有ATM +/ -和ATM - / -等位基因的小鼠比目鱼肌中是正常的。然而，胰岛素不会刺激ATM - / -比目鱼肌中的葡萄糖转运或AS160的磷酸化。野生型EDL的ATM蛋白水平明显高于野生型比目鱼。在ATM - / -小鼠的指长伸肌（EDL）中，胰岛素不刺激葡萄糖运输。然而,比目鱼肌与发现,刺激一种蛋白激酶磷酸化在ATM /−−EDL钝化,伴随的倾向刺激磷脂酰肌醇3-kinase活动一起下降,研究结果表明,ATM在刺激葡萄糖运输过程中发挥作用的AS160在肌肉组成的慢速和快速oxidative-glycolytic纤维(比目鱼肌),包含快速糖酵解肌肉纤维的一种蛋白激酶水平(EDL)。
There are reports that ataxia telangiectasia mutated (ATM) plays a role in insulin-stimulated Akt phosphorylation, though in some cell types this is not the case. As Akt plays a key role in insulin signaling leading to glucose transport in skeletal muscle, the predominant tissue in insulin-stimulated glucose disposal, we examined whether insulin-stimulated Akt phosphorylation and/or glucose transport would be decreased in skeletal muscle of mice lacking functional ATM compared to muscle from wild-type mice. We found that in vitro insulin-stimulated Akt phosphorylation was normal in soleus muscle from mice with one functional allele of ATM (ATM +/−) and from ATM −/− mice. However, insulin did not stimulate glucose transport or phosphorylation of AS160 in ATM −/− soleus. ATM protein level was markedly higher in wild type EDL than in wild type soleus. In extensor digitorum longus (EDL) from ATM −/− mice, insulin did not stimulate glucose transport. However, in contrast to findings for soleus, insulin-stimulated Akt phosphorylation was blunted in ATM −/− EDL, concomitant for a tendency for insulin-stimulated phosphatidylinositol 3-kinase activity to be decreased Together, the findings suggest that ATM plays a role in insulin-stimulated glucose transport at the level of AS160 in muscle comprised of slow and fast oxidative-glycolytic fibers (soleus) and at the level of Akt in muscle containing fast glycolytic fibers (EDL).
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影响因子：
2.7
作者：
Ching, James Kain;Luebbert, Stephen H.;Fisher, Jonathan S.
通讯作者：
Fisher, Jonathan S.
影响因子：
4.8
作者：
O'Neill, T;Dwyer, AJ;Rathbun, GA
通讯作者：
Rathbun, GA
DOI：
10.1016/j.bbrc.2011.01.075
发表时间：
2011-02-25
影响因子：
3.1
作者：
Patel, Akshar Y.;McDonald, Todd M.;Fisher, Jonathan S.
通讯作者：
Fisher, Jonathan S.
影响因子：
6.5
作者：
Razani, Babak;Feng, Chu;Semenkovich, Clay F.
通讯作者：
Semenkovich, Clay F.
影响因子：
158.5
作者：
SHULMAN, GI;ROTHMAN, DL;SHULMAN, RG
通讯作者：
SHULMAN, RG