Viollet Benoit, Andreelli Fabrizio
Inserm, U1016, Institut Cochin, Paris, France.
Handb Exp Pharmacol. 2011(203):303-30. doi: 10.1007/978-3-642-17214-4_13.
AMP-activated protein kinase AMP-activated protein kinase (AMPK AMPK ), a phylogenetically conserved serine/threonine protein kinase, is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. It is now recognized that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile, and blood pressure in insulin-resistant rodents. Indeed, AMPK activation mimics the beneficial effects of physical activity or those of calorie restriction calorie restriction by acting on multiple cellular targets. In addition, it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs drugs including the biguanides (metformin metformin ) and thiazolidinedione thiazolidinedione s, as well as of insulin-sensitizing adipokines (e.g., adiponectin adiponectin ). Taken together, such findings highlight the logic underlying the concept of targeting the AMPK pathway for the treatment of metabolic syndrome and type 2 diabetes.
AMP激活的蛋白激酶（AMPK）是一种在系统发育上保守的丝氨酸/苏氨酸蛋白激酶，是细胞和全身能量稳态的主要调节因子，它协调代谢途径以平衡营养供应与能量需求。现在人们认识到，在胰岛素抵抗的啮齿动物中，AMPK的药理学激活可改善血糖稳态、血脂状况和血压。事实上，AMPK激活通过作用于多个细胞靶点，模拟了体育活动或热量限制的有益效果。此外，现已证明，AMPK是包括双胍类药物（二甲双胍）和噻唑烷二酮类药物以及胰岛素增敏脂肪因子（如脂联素）在内的主要抗糖尿病药物的可能（尽管是间接）靶点之一。综上所述，这些发现凸显了针对AMPK途径治疗代谢综合征和2型糖尿病这一概念背后的逻辑。
