BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis

By R. Rudic, P. McNamara, A. Curtis, R. Boston, Satchidananda Panda, John B. Hogenesch, G. FitzGerald. PLoS Biology, 2004

1,072 citations recorded by the source corpus.

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.

Subfields: Endocrine and Autonomic Systems, Plant Science

View Paper: https://www.semanticscholar.org/paper/f3e4f833595ace57fa76721c57f3b82d588fe063

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. J. Takahashi
2. C. H. Ko
3. J. Y. Chiang
4. Tiangang Li
5. Gerald I. Shulman
6. Erin L. McDearmon
7. Heekyung Hong

In Plant Science

1. J. Takahashi
2. C. H. Ko
3. Gerald I. Shulman
4. Craig B. Thompson

Citations in the corpus

• Light at night increases body mass by shifting the time of food intake (2010, background): “Because multiple studies have linked disruption of the molecular circadian clock and metabolic disorders (10, 12, 14), we hypothesized that LAN exposure alters circadian organization and affects metabolic parameters.”
• Bile Acid Signaling in Metabolic Disease and Drug Therapy (2014, background): “Bmal1 and Clock are involved in glucose metabolism (Rudic et al., 2004).”
• Reprogramming of the Circadian Clock by Nutritional Challenge (2013, neutral): “Metabolic homeostasis is not maintained when components of the circadian clock are missing or functioning improperly (Kondratov et al., 2006; Lee et al., 2011; Marcheva et al., 2010; Rudic et al., 2004; Sadacca et al., 2011; Shi et al., 2013; Turek et al., 2005; Zhang et al., 2010) and circadian dis”
• Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice (2010, background): “This is not a trivial point, as changes to circadian rhythms have been shown to affect glucose metabolism (Rudic et al., 2004; Turek et al., 2005; Kohsaka and Bass, 2007).”
• Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. (2006, background): “In addition, the recently reported role of BMAL1 in glucose homeostasis and impaired glucose tolerance and insulin sensitivity in Bmal1−/− animals (Rudic et al. 2004) suggests a possible connection between the circadian system and the insulin/insulin growth factor (IGF) pathways, which are known to…”
• Metabolic regulation of epigenetics (2012, background): “Bmal1 / and Clockmut mice exhibit various abnormalities of glucose and lipid homeostasis (Oishi et al., 2006; Rudic et al., 2004; Turek et al., 2005).”