Delays in insulin signaling towards glucose disposal in human skeletal muscle
Delays in insulin signaling towards glucose disposal in human skeletal muscle
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DOI：
10.1677/joe.0.1720645
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发表时间：
2002-03-01
影响因子：
4
通讯作者：
Klein, HH
中科院分区：
文献类型：
--
作者：
Grimmsmann, T;Levin, K;Klein, HH
我们探索了血浆胰岛素升高和葡萄糖代谢增加之间的延迟是否发生在被认为是胰岛素信号级联一部分的步骤之前、步骤处或步骤下游。16例非糖尿病受试者在正常血糖高胰岛素葡萄糖钳夹试验前、血浆胰岛素水平升高20分钟和180分钟后进行骨骼肌活检。虽然血浆胰岛素在10min内达到终浓度的98%，但在20in-in时，胰岛素受体激酶(IRK)活性、与胰岛素受体底物-1(IRS-1)相关的P85活性、IRS-1相关的磷脂酰肌醇3-激酶(PI3K)活性和Thr(308)-蛋白激酶B(PKB)磷酸化分别仅为180min时的60%、48%、34%和47%。这表明在irk水平之前存在延迟，而irk和PKB激活之间的延迟很小或没有延迟。观察到糖原合成酶活性和葡萄糖处置在20min时都只达到了180min时各自值的25%，这表明所研究的信号步骤下游还有额外的延迟。
We explored whether the delay that occurs between a rise in plasma insulin and the increase of glucose disposal occurs before, at, or downstream of steps that are believed to be part of the insulin signaling cascade. Skeletal muscle biopsies were obtained from 16 nondiabetic subjects before, and 20 and 180 min after plasma insulin levels had been augmented in euglycemic hyperinsulinemic glucose clamps. Although plasma insulin had reached 98% of its final concentration within 10 min, insulin receptor kinase (IRK) activity, p85 associated with insulin receptor substrate-1 (IRS-1), IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity, and Thr(308)-protein kinase B (PKB) phosphorylation in the muscle biopsies at 20 in-in had reached only 60, 48, 34 and 47% respectively of those at 180 min. This suggests a delay before the level of IRK and little or no delay between IRK and PKB activation. The observation that glycogen synthase activity and glucose disposal at 20 min had both only reached 25% of the respective values at 180 min suggests an additional delay downstream of the investigated signaling steps.