Højlund Kurt, Mustard Kirsty J, Staehr Peter, Hardie D Grahame, Beck-Nielsen Henning, Richter Erik A, Wojtaszewski Jørgen F P
Department of Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E239-44. doi: 10.1152/ajpendo.00326.2003. Epub 2003 Oct 7.
Acute or chronic activation of AMP-activated protein kinase (AMPK) increases insulin sensitivity. Conversely, reduced expression and/or function of AMPK might play a role in insulin resistance in type 2 diabetes. Thus protein expression of the seven subunit isoforms of AMPK and activities and/or phosphorylation of AMPK and acetyl-CoA carboxylase-beta (ACCbeta) was measured in skeletal muscle from obese type 2 diabetic and well-matched control subjects during euglycemic-hyperinsulinemic clamps. Protein expression of all AMPK subunit isoforms (alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3) in muscle of obese type 2 diabetic subjects was similar to that of control subjects. In addition, alpha1- and alpha2-associated activities of AMPK, phosphorylation of alpha-AMPK subunits at Thr172, and phosphorylation of ACCbeta at Ser221 showed no difference between the two groups and were not regulated by physiological concentrations of insulin. These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity.
AMP 激活的蛋白激酶（AMPK）的急性或慢性激活可提高胰岛素敏感性。相反，AMPK 的表达降低和/或功能受损可能在 2 型糖尿病的胰岛素抵抗中起作用。因此，在正常血糖 - 高胰岛素钳夹期间，对肥胖 2 型糖尿病患者和匹配良好的对照受试者的骨骼肌中 AMPK 的七种亚基异构体的蛋白表达以及 AMPK 和乙酰辅酶 A 羧化酶 -β（ACCβ）的活性和/或磷酸化进行了测量。肥胖 2 型糖尿病患者肌肉中所有 AMPK 亚基异构体（α1、α2、β1、β2、γ1、γ2 和 γ3）的蛋白表达与对照受试者相似。此外，AMPK 的 α1 和 α2 相关活性、α-AMPK 亚基在 Thr172 处的磷酸化以及 ACCβ 在 Ser221 处的磷酸化在两组之间没有差异，并且不受生理浓度胰岛素的调节。这些数据表明，肥胖 2 型糖尿病患者骨骼肌中胰岛素对糖原合成和脂质氧化的作用受损不太可能涉及 AMPK 表达和活性的变化。
