BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis.
BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis.
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DOI：
10.1371/journal.pbio.0020377
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发表时间：
2004-11
期刊：
影响因子：
9.8
通讯作者：
Fitzgerald GA
中科院分区：
文献类型：
--
作者：
Rudic RD;McNamara P;Curtis AM;Boston RC;Panda S;Hogenesch JB;Fitzgerald GA
生物钟是通过一系列独特的自我调节相互作用产生的，称为分子钟。受分子钟影响的行为节律得到了很好的表征。我们证明了Bmal1和时钟在葡萄糖稳态调节中的作用。已知的生物钟成分Bmal1（Mop3）和Clock的失活抑制了葡萄糖和甘油三酯的昼夜变化。葡萄糖异生被废除Bmal1的删除，并在时钟突变体中被抑制，但皮质酮和胰高血糖素对胰岛素诱导的低血糖的反调节反应被保留。此外，高脂饮食通过放大葡萄糖耐量和胰岛素敏感性的昼夜变化来调节碳水化合物代谢，并且Clock突变恢复了进食型。Bmal 1和Clock基因在核心分子时钟中发挥作用，对胰岛素诱导的低血糖的恢复起着深刻的控制作用。此外，异步饮食提示可能通过与外周分子钟的相互作用来改变葡萄糖稳态。除了调节各种行为节律外，分子钟还在葡萄糖稳态的控制中发挥作用
Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and is depressed in Clock mutants, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycaemia is retained. Furthermore, a high-fat diet modulates carbohydrate metabolism by amplifying circadian variation in glucose tolerance and insulin sensitivity, and mutation of Clock restores the chow-fed phenotype. Bmal1 and Clock, genes that function in the core molecular clock, exert profound control over recovery from insulin-induced hypoglycaemia. Furthermore, asynchronous dietary cues may modify glucose homeostasis via their interactions with peripheral molecular clocks. Besides regulating various behavioral rhythms, the molecular clock plays a role in the control of glucose homeostasis
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