| Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 in antidiabetic therapy. | |
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MedLine Citation:
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PMID: 21484570 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Glucocorticoid action is mediated by glucocorticoid receptor (GR), which upon cortisol binding is activated and regulates the transcriptional expression of target genes and downstream physiological functions. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to active cortisol. Since cortisol is also produced through biosynthesis in the adrenal glands, the total cortisol level in a given tissue is determined by both the circulating cortisol concentration and the local 11β-HSD1 activity. 11β-HSD1 is expressed in liver, adipose, brain, and placenta. Since it contributes to the local cortisol levels in these tissues, 11β-HSD1 plays a critical role in glucocorticoid action. The metabolic symptoms caused by glucocorticoid excess in Cushing's syndrome overlap with the characteristics of the metabolic syndrome, suggesting that increased glucocorticoid activity may play a role in the etiology of the metabolic syndrome. Consistent with this notion, elevated adipose expression of 11β-HSD1 induced metabolic syndrome-like phenotypes in mice. Thus, 11β-HSD1 is a proposed therapeutic target to normalize glucocorticoid excess in a tissue-specific manner and mitigate obesity and insulin resistance. Selective inhibitors of 11β-HSD1 are under development for the treatment of type 2 diabetes and other components of the metabolic syndrome. |
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Authors:
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Minghan Wang |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Handbook of experimental pharmacology Volume: - ISSN: 0171-2004 ISO Abbreviation: Handb Exp Pharmacol Publication Date: 2011 |
Date Detail:
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Created Date: 2011-04-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902231 Medline TA: Handb Exp Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 127-46 Citation Subset: IM |
Affiliation:
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Department of Metabolic Disorders, Amgen Inc., One Amgen Center Drive, Mail Stop 29-1-A, Thousand Oaks, CA, 91320, USA, mwang@amgen.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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