Lai Yu-Chiang, Zarrinpashneh Elham, Jensen Jørgen
Department of Physiology, National Institute of Occupational Health, Oslo, Norway.
J Appl Physiol (1985). 2010 May;108(5):1106-15. doi: 10.1152/japplphysiol.00401.2009. Epub 2010 Feb 25.
Insulin and contraction regulate glucose uptake and glycogen synthase (GS) via distinct mechanisms in skeletal muscles, and an additive effect has been reported. Glycogen content is known to influence both contraction- and insulin-stimulated glucose uptake and GS activity. Our study reports that contraction and insulin additively stimulate glucose uptake in rat epitrochlearis muscles with normal (NG) and high (HG) glycogen contents, but the additive effect was only partial. In muscles with low glycogen (LG) content no additive effect was seen, but glucose uptake was higher in LG than in NG and HG during contraction, insulin stimulation, and when the two stimuli were combined. In LG, contraction-stimulated AMP-activated protein kinase (AMPK) activity and insulin-stimulated PKB phosphorylation were higher than in NG and HG, but phosphorylation of Akt substrate of 160 kDa was not elevated correspondingly. GLUT4 content was 50% increased in LG (rats fasted 24 h), which may explain the increased glucose uptake. Contraction and insulin also additively increased GS fractional activity in NG and HG but not in LG. GS fractional activity correlated most strongly with GS Ser641 phosphorylation (R -0.94, P<0.001). GS fractional activity also correlated with GS Ser7,10 phosphorylation, but insulin did not reduce GS Ser7,10 phosphorylation. In conclusion, an additive effect of contraction and insulin on glucose uptake and GS activity occurs in muscles with normal and high glycogen content but not in muscles with low glycogen content. Furthermore, contraction, insulin, and glycogen content all regulate GS Ser641 phosphorylation and GS fractional activity in concert.
胰岛素和收缩通过不同机制调节骨骼肌中的葡萄糖摄取和糖原合酶（GS），且已有报道称存在相加效应。已知糖原含量会影响收缩和胰岛素刺激的葡萄糖摄取以及GS活性。我们的研究报告称，收缩和胰岛素对糖原含量正常（NG）和高（HG）的大鼠肱三头肌葡萄糖摄取具有相加刺激作用，但这种相加效应只是部分的。在糖原含量低（LG）的肌肉中未观察到相加效应，但在收缩、胰岛素刺激以及两种刺激联合作用时，LG中的葡萄糖摄取高于NG和HG。在LG中，收缩刺激的AMP活化蛋白激酶（AMPK）活性和胰岛素刺激的蛋白激酶B（PKB）磷酸化高于NG和HG，但160 kDa的Akt底物磷酸化并未相应升高。LG（禁食24小时的大鼠）中的葡萄糖转运蛋白4（GLUT4）含量增加了50%，这可能解释了葡萄糖摄取增加的原因。收缩和胰岛素对NG和HG中的GS分数活性也有相加增加作用，但对LG则没有。GS分数活性与GS Ser641磷酸化的相关性最强（R = -0.94，P<0.001）。GS分数活性也与GS Ser7,10磷酸化相关，但胰岛素并未降低GS Ser7,10磷酸化。总之，收缩和胰岛素对葡萄糖摄取和GS活性的相加效应发生在糖原含量正常和高的肌肉中，而不是糖原含量低的肌肉中。此外，收缩、胰岛素和糖原含量共同调节GS Ser641磷酸化和GS分数活性。
