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

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 clo...

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Main Authors: Rudic, R. Daniel, McNamara, Peter, Curtis, Anne-Maria, Boston, Raymond C, Panda, Satchidananda, Hogenesch, John B, FitzGerald, Garret A
Format: Online
Language:English
Published: Public Library of Science 2004
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524471/
id pubmed-524471
recordtype oai_dc
spelling pubmed-5244712004-11-02 BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis Rudic, R. Daniel McNamara, Peter Curtis, Anne-Maria Boston, Raymond C Panda, Satchidananda Hogenesch, John B FitzGerald, Garret A Research Article 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. Public Library of Science 2004-11 2004-11-02 /pmc/articles/PMC524471/ /pubmed/15523558 http://dx.doi.org/10.1371/journal.pbio.0020377 Text en Copyright: © 2004 Rudic et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Rudic, R. Daniel
McNamara, Peter
Curtis, Anne-Maria
Boston, Raymond C
Panda, Satchidananda
Hogenesch, John B
FitzGerald, Garret A
spellingShingle Rudic, R. Daniel
McNamara, Peter
Curtis, Anne-Maria
Boston, Raymond C
Panda, Satchidananda
Hogenesch, John B
FitzGerald, Garret A
BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis
author_facet Rudic, R. Daniel
McNamara, Peter
Curtis, Anne-Maria
Boston, Raymond C
Panda, Satchidananda
Hogenesch, John B
FitzGerald, Garret A
author_sort Rudic, R. Daniel
title BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis
title_short BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis
title_full BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis
title_fullStr BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis
title_full_unstemmed BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis
title_sort bmal1 and clock, two essential components of the circadian clock, are involved in glucose homeostasis
description 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.
publisher Public Library of Science
publishDate 2004
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524471/
_version_ 1611369734884818944

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