Musi Nicolas, Goodyear Laurie J
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Womens's Hospital, Harvard Medical School, Boston, MA, USA.
Curr Drug Targets Immune Endocr Metabol Disord. 2002 Jul;2(2):119-27.
The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated in response to conditions of cellular stress such as muscle contraction and hypoxia. In skeletal muscle, activation of AMPK leads to increased glucose uptake, enhanced insulin sensitivity and oxidation of fatty acids. In the liver, AMPK activation causes an increase in fatty acid oxidation and inhibition of glucose production. These effects on glucose and fat metabolism make AMPK an important pharmacological target for the treatment of type 2 diabetes. Studies done in animal models of type 2 diabetes have shown that pharmacological activation of AMPK with the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) decreases blood glucose and insulin concentrations. While strong efforts are underway in order to identify novel AMPK-activating compounds, the safety of chronic pharmacological activation of AMPK remains to be determined.
AMP激活的蛋白激酶（AMPK）是一种能量感应酶，在诸如肌肉收缩和缺氧等细胞应激条件下被激活。在骨骼肌中，AMPK的激活会导致葡萄糖摄取增加、胰岛素敏感性增强以及脂肪酸氧化。在肝脏中，AMPK激活会使脂肪酸氧化增加并抑制葡萄糖生成。这些对葡萄糖和脂肪代谢的影响使AMPK成为治疗2型糖尿病的重要药理学靶点。在2型糖尿病动物模型中进行的研究表明，用化合物5-氨基咪唑-4-甲酰胺核糖核苷（AICAR）对AMPK进行药理学激活可降低血糖和胰岛素浓度。虽然目前正在大力努力寻找新型AMPK激活化合物，但AMPK慢性药理学激活的安全性仍有待确定。
