Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
Acta Physiol (Oxf). 2009 May;196(1):129-45. doi: 10.1111/j.1748-1716.2009.01968.x. Epub 2009 Feb 19.
The worldwide prevalence of type 2 diabetes (T2D) and related disorders of the metabolic syndrome (MS) has reached epidemic proportions. Insulin resistance (IR) is a major perturbation that characterizes these disorders. Extra-adipose accumulation of lipid, particularly within the liver and skeletal muscle, is closely linked with the development of IR. The AMP-activated protein kinase (AMPK) pathway plays an important role in the regulation of both lipid and glucose metabolism. Through its effects to increase fatty acid oxidation and inhibit lipogenesis, AMPK activity in the liver and skeletal muscle could be expected to ameliorate lipid accumulation and associated IR in these tissues. In addition, AMPK promotes glucose uptake into skeletal muscle and suppresses glucose output from the liver via insulin-independent mechanisms. These characteristics make AMPK a highly attractive target for the development of strategies to curb the prevalence and costs of T2D. Recent insights into the regulation of AMPK and mechanisms by which it modulates fuel metabolism in liver and skeletal muscle are discussed here. In addition, we consider the arguments for and against the hypothesis that dysfunctional AMPK contributes to IR. Finally we review studies which assess AMPK as an appropriate target for the prevention and treatment of T2D and MS.
全世界 2 型糖尿病（T2D）和相关代谢综合征（MS）的流行程度已经达到了流行的程度。胰岛素抵抗（IR）是这些疾病的主要特征。脂肪在脂肪组织外的蓄积，特别是在肝脏和骨骼肌中，与 IR 的发生密切相关。AMP 激活的蛋白激酶（AMPK）途径在调节脂质和葡萄糖代谢方面起着重要作用。通过增加脂肪酸氧化和抑制脂肪生成，预计肝脏和骨骼肌中的 AMPK 活性可以改善这些组织中的脂质蓄积和相关的 IR。此外，AMPK 通过非胰岛素依赖的机制促进骨骼肌摄取葡萄糖，并抑制肝脏葡萄糖输出。这些特性使得 AMPK 成为抑制 T2D 发病率和成本的策略的极具吸引力的靶点。本文讨论了 AMPK 的调节以及它在肝脏和骨骼肌中调节燃料代谢的机制的最新见解。此外，我们还考虑了 AMPK 功能障碍是否导致 IR 的假说。最后，我们回顾了评估 AMPK 作为预防和治疗 T2D 和 MS 的适当靶点的研究。
