AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes
AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes
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DOI：
10.1152/ajpendo.00326.2003
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发表时间：
2004-02-01
影响因子：
5.1
通讯作者：
Wojtaszewski, JFP
中科院分区：
文献类型：
--
作者：
Hojlund, K;Mustard, KJ;Wojtaszewski, JFP
AMP活化蛋白激酶（AMPK）的急性或慢性活化增加胰岛素敏感性。相反，AMPK的表达和/或功能降低可能在2型糖尿病的胰岛素抵抗中起作用。因此，在正常血糖-高胰岛素钳夹过程中，在肥胖2型糖尿病和匹配良好的对照受试者的骨骼肌中测量AMPK的七种亚基同种型的蛋白质表达和AMPK和乙酰辅酶A羧化酶-β（ACC β）的活性和/或磷酸化。肥胖2型糖尿病患者肌肉中AMPK亚基亚型（α 1、α 2、β 1、β 2、γ 1、γ 2和γ 3）的蛋白表达与对照组相似。此外，AMPK的α 1和α 2相关活性、α-AMPK亚基在Thr（172）的磷酸化和ACC β在Ser（221）的磷酸化在两组之间没有差异，并且不受胰岛素生理浓度的调节。这些数据表明，受损的胰岛素对糖原合成和脂肪氧化的作用，在肥胖的2型糖尿病受试者的骨骼肌不太可能涉及AMPK的表达和活性的变化。
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 acetylCoA 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 Thr(172), and phosphorylation of ACCbeta at Ser(221) 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.