Glucocorticoid regulation of the circadian clock modulates glucose homeostasis.

Full Abstract

Circadian clock genes are regulated by glucocorticoids; however, whether this regulation is a direct or secondary effect and the physiological consequences of this regulation were unknown. Here, we identified glucocorticoid response elements (GREs) at multiple clock genes and showed that 3 were directly regulated by the glucocorticoid receptor. We determined that a GRE within the core clock gene Per2 was continuously occupied during rhythmic expression and essential for glucocorticoid regulation of that gene in vivo. We further demonstrated that mice with a genomic deletion spanning this GRE expressed elevated leptin levels and were protected from glucose intolerance and insulin resistance on glucocorticoid treatment but not from muscle wasting. We conclude that Per2 is an integral component of a particular glucocorticoid regulatory pathway and that glucocorticoid regulation of the peripheral clock is selectively required for some actions of glucocorticoids.

Author information

Author/s: So, Alex Y -L (AY); Bernal, Teresita U (TU); Pillsbury, Marlisa L (ML); Yamamoto, Keith R (KR); Feldman, Brian J (BJ);

Affiliation: Department of Pediatrics, University of California, 513 Parnassus Drive, San Francisco, CA 94143, USA.

Grants: CA 20535 (Agency:NCI NIH HHS) ; DK 73697 (Agency:NIDDK NIH HHS) ; GM 56847 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Oct; vol 106 (issue 41) : pp 17582-7

Dates: Created 2009/10/15; Completed 2009/11/03;

PMID: 19805059, status: MEDLINE (last retrieval date: 11/3/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Cell Cycle Proteins - genetics
Circadian Rhythm - drug effects; genetics
Gene Expression Regulation
Glucocorticoids - pharmacology; physiology
Glucose - metabolism
Homeostasis

Associated Chemicals: Bhlhb3 protein, mouse (0) ; Cell Cycle Proteins (0) ; Glucocorticoids (0) ; Leptin (0) ; Nuclear Proteins (0) ; Per2 protein, mouse (0) ; Transcription Factors (0) ; Glucose (50-99-7)

These are the highest related articles currently in the database: