Coderre Lise, Vallega Gino A, Pilch Paul F, Chipkin Stuart R
The Montreal Diabetes Research Centre, Centre hospitalier de l'Université de Montréal (CHUM)-Hôtel-Dieu and Department of Medicine, Université de Montréal, 3850 St. Urbain, Montréal, Que., Canada H2W 1T8.
Arch Biochem Biophys. 2007 Aug 1;464(1):144-50. doi: 10.1016/j.abb.2007.04.012. Epub 2007 May 2.
The aim of this study was to investigate the effect of insulin resistance on glycogen concentration and glycogen synthase activity in the red and white gastrocnemius muscles and to determine whether the inverse relationship existing between glycogen concentration and enzyme activity is maintained in insulin resistant state. These questions were addressed using 3 models that induce various degrees of insulin resistance: sucrose feeding, dexamethasone administration, and a combination of both treatments (dex+sucrose). Sucrose feeding raised triglyceride levels without affecting plasma glucose or insulin concentrations whereas dexamethasone and dex+sucrose provoked severe hyperinsulinemia, hyperglycemia and hypertriglyceridemia. Sucrose feeding did not alter muscle glycogen concentration but provoked a small reduction in the glycogen synthase activity ratio (-/+ glucose-6-phosphate) in red but not in white gastrocnemius. Dexamethasone administration augmented glycogen concentration and reduced glycogen synthase activity ratio in both muscle fiber types. In contrast, dex+sucrose animals showed decreased muscle glycogen concentration compared to dexamethasone group, leading to levels similar to those of control animals. This was associated with lower glycogen synthase activity compared to control animals leading to levels comparable to those of dexamethasone-treated animals. Thus, in dex+sucrose animals, the inverse relationship observed between glycogen levels and glycogen synthase activity was not maintained, suggesting that factors other than the glycogen concentration modulate the enzyme's activity. In conclusion, while insulin resistance was associated with a reduced glycogen synthase activity ratio, we found no correlation between muscle glycogen concentration and insulin resistance. Furthermore, our results suggest that sucrose treatment may modulate dexamethasone action in skeletal muscle.
本研究的目的是探讨胰岛素抵抗对红白腓肠肌糖原浓度和糖原合酶活性的影响,并确定在胰岛素抵抗状态下糖原浓度与酶活性之间存在的反比关系是否得以维持。使用三种诱导不同程度胰岛素抵抗的模型来解决这些问题:蔗糖喂养、地塞米松给药以及两种处理方式的联合(地塞米松+蔗糖)。蔗糖喂养可提高甘油三酯水平,而不影响血浆葡萄糖或胰岛素浓度,而地塞米松和地塞米松+蔗糖则引发严重的高胰岛素血症、高血糖症和高甘油三酯血症。蔗糖喂养不会改变肌肉糖原浓度,但会使红腓肠肌而非白腓肠肌中糖原合酶活性比值(-/+葡萄糖-6-磷酸)略有降低。地塞米松给药会增加两种肌纤维类型中的糖原浓度并降低糖原合酶活性比值。相比之下,与地塞米松组相比,地塞米松+蔗糖组动物的肌肉糖原浓度降低,导致其水平与对照动物相似。这与对照动物相比糖原合酶活性较低有关,导致其水平与地塞米松处理动物相当。因此,在地塞米松+蔗糖组动物中,未维持糖原水平与糖原合酶活性之间观察到的反比关系,这表明除糖原浓度外的其他因素调节了该酶的活性。总之,虽然胰岛素抵抗与糖原合酶活性比值降低有关,但我们发现肌肉糖原浓度与胰岛素抵抗之间没有相关性。此外,我们的结果表明蔗糖处理可能会调节地塞米松在骨骼肌中的作用。