Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases
Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases
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DOI：
10.1080/13813450600935263
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发表时间：
2006-07-01
影响因子：
3
通讯作者：
Holness, Mark J.
中科院分区：
文献类型：
--
作者：
Sugden, Mary C.;Holness, Mark J.
控制哺乳动物丙酮酸脱氢酶复合物 (PDC) 活性的机制包括丙酮酸脱氢酶激酶 (PDK 1-4) 家族对其进行磷酸化（失活）。在此，我们回顾了与葡萄糖和脂质稳态相关的 PDK（特别是 PDK2 和 PDK4）的活性和表达调节的新进展。本综述描述了与 PDK 的急性和长期调节模式相关的最新进展，特别强调核受体的调节作用，包括过氧化物酶体增殖物激活受体 (PPAR) α 和肝脏 X 受体 (LXR)、PPAR γ 辅激活剂 α (PGC-1 α) 和胰岛素，以及 PDK 活性和表达变化对葡萄糖和脂质稳态的影响。由于当脂质输送和氧化之间存在不平衡时，PDK4 可能有助于脂质清除，因此它可能是旨在纠正疾病状态下异常脂质和葡萄糖稳态的干预措施的一个有吸引力的目标。
The mechanisms that control mammalian pyruvate dehydrogenase complex (PDC) activity include its phosphorylation (inactivation) by a family of pyruvate dehydrogenase kinases (PDKs 1-4). Here we review new developments in the regulation of the activities and expression of the PDKs, in particular PDK2 and PDK4, in relation to glucose and lipid homeostasis. This review describes recent advances relating to the acute and long-term modes of regulation of the PDKs, with particular emphasis on the regulatory roles of nuclear receptors including peroxisome proliferator-activated receptor (PPAR) alpha and Liver X receptor (LXR), PPAR gamma coactivator alpha (PGC-1 alpha) and insulin, and the impact of changes in PDK activity and expression in glucose and lipid homeostasis. Since PDK4 may assist in lipid clearance when there is an imbalance between lipid delivery and oxidation, it may represent an attractive target for interventions aimed at rectifying abnormal lipid as well as glucose homeostasis in disease states.