Li Minghua, Li Chunmei, Parkhouse Wade S
Metabolic Biochemistry Lab, School of Kinesiology, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.
Mech Ageing Dev. 2003 Jul;124(7):771-8. doi: 10.1016/s0047-6374(03)00124-6.
The ability of des IGF-I to activate Akt-1 and p70 S6K in skeletal muscle with or without acute endurance exercise was examined in young and old mice. Mice were sacrificed 12 h after a moderate intensity treadmill run following an interperitoneal injection of des-IGF-I or saline. Blood and skeletal muscle were collected and IGF-I receptor, Akt-1 and p70 S6K protein contents and their phosphorylation status were determined. Injection of des IGF-I similarly decreased plasma glucose concentration in both young (P<0.01) and old mice (P<0.01) whereas plasma insulin and total IGF-I levels of young and old mice were not significantly changed by des IGF-I. Total IGF-I receptor protein and IGF-1 receptor phosphorylation were lower in aged mice (P<0.05). Basal phosphorylation of Akt-1 was lower in aged skeletal muscle (P<0.01) and this was not caused by changes in Akt-1 protein. In both young (P<0.01) and aged (P<0.05) mice, des IGF-I significantly increased the phosphorylation of Akt-1 at Ser 473. However, a des IGF-I-mediated increase in the p70 S6K phosphorylation (P<0.01) was only seen in young mice. Prior exercise decreased the total plasma IGF-I level in the presence of des IGF-I in aged mice. Des IGF-I-mediated Akt-1 and p70 S6K phosphorylation was not changed by exercise in either young or old mice. It is concluded that there was an aging-related resistance at the p70 S6K level in mouse skeletal muscle that could not be restored by prior exercise and this resistance is associated with lower IGF-I receptor number and Akt-1 phosphorylation in the aged skeletal muscle.
在年轻和老年小鼠中，研究了脱碘胰岛素样生长因子-I（des IGF-I）在有或无急性耐力运动情况下激活骨骼肌中Akt-1和p70 S6K的能力。在腹腔注射des-IGF-I或生理盐水后，小鼠进行中等强度跑步机跑步，12小时后处死。收集血液和骨骼肌，测定胰岛素样生长因子-I受体、Akt-1和p70 S6K蛋白含量及其磷酸化状态。注射des IGF-I同样降低了年轻小鼠（P<0.01）和老年小鼠（P<0.01）的血浆葡萄糖浓度，而des IGF-I对年轻和老年小鼠的血浆胰岛素和总胰岛素样生长因子-I水平没有显著影响。老年小鼠的总胰岛素样生长因子-I受体蛋白和胰岛素样生长因子-1受体磷酸化水平较低（P<0.05）。老年骨骼肌中Akt-1的基础磷酸化水平较低（P<0.01），这不是由Akt-1蛋白的变化引起的。在年轻小鼠（P<0.01）和老年小鼠（P<0.05）中，des IGF-I均显著增加了Akt-1在Ser 473位点的磷酸化。然而，des IGF-I介导的p70 S6K磷酸化增加（P<0.01）仅在年轻小鼠中观察到。预先运动降低了老年小鼠在des IGF-I存在情况下的总血浆胰岛素样生长因子-I水平。des IGF-I介导的Akt-1和p70 S6K磷酸化在年轻或老年小鼠中均不受运动影响。结论是，小鼠骨骼肌中存在与衰老相关的p70 S6K水平抗性，预先运动无法恢复这种抗性，且这种抗性与老年骨骼肌中较低的胰岛素样生长因子-I受体数量和Akt-1磷酸化有关。
