Musi Nicolas
Diabetes Division, University of Texas Health Science Center at San Antonio and the Texas Diabetes Institute, San Antonio, TX 78207, USA.
Curr Med Chem. 2006;13(5):583-9. doi: 10.2174/092986706776055724.
AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge, being activated in situations of high-energy phosphate depletion. Upon activation, AMPK functions to restore cellular ATP by modifying diverse metabolic pathways. AMPK is activated robustly by skeletal muscle contraction and myocardial ischemia, and may be involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and in decreased production of glucose, cholesterol, and triglycerides. Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
AMP激活的蛋白激酶（AMPK）是一种充当能量传感器的酶，在高能磷酸耗竭的情况下被激活。激活后，AMPK通过调节多种代谢途径来恢复细胞内的ATP。骨骼肌收缩和心肌缺血可强烈激活AMPK，它可能参与了这些刺激所产生的葡萄糖转运和脂肪酸氧化的刺激过程。在肝脏中，AMPK的激活会导致脂肪酸氧化增强，以及葡萄糖、胆固醇和甘油三酯的生成减少。最近的研究表明，AMPK是二甲双胍和噻唑烷二酮等药物许多代谢作用的细胞介质，也是具有胰岛素增敏作用的脂肪细胞因子瘦素和脂联素的细胞介质。这些数据，以及体内用5-氨基咪唑-4-甲酰胺核苷（AICAR）对AMPK进行化学激活可改善血糖浓度和血脂谱的研究证据，使这种酶成为治疗2型糖尿病和其他代谢紊乱的有吸引力的药理学靶点。
