The Role of 11Beta-Hydroxysteroid Dehydrogenase in Metabolic Disease and Therapeutic Potential of 11Beta-HSD1 Inhibitors

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Abstract:

Glucocorticoids play an essential role in the regulation of multiple physiological processes, including energy metabolism, maintenance of blood pressure and stress responses, as well as cognitive functions. On a tissue-specific level, glucocorticoid action is controlled by 11beta-hydroxysteroid dehydrogenase enzymes. The type 1 enzyme (11beta-HSD1) is a NADP(H)-dependent bidirectional enzyme in vitro and reduces cortisone to active cortisol in vivo. 11beta-HSD1 is expressed in many tissues including the liver, adipose and skeletal muscles. Chronically elevated local glucocorticoid action as a result of increased 11beta-HSD1 activity has been associated with the metabolic syndrome, which is characterized by obesity, insulin resistance, type 2 diabetes and cardiovascular complications. Recent studies indicate that the inhibition of 11beta-HSD1 mitigates the adverse effects of excessive glucocorticoid levels on metabolic parameters and provides promising opportunities for the development of therapeutic interventions. This review discusses recently disclosed 11beta-HSD1 inhibitors and their potential for the treatment of metabolic disorders.

Keywords: 11beta-HSD1; diabetes; glucocorticoid; metabolic syndrome; obesity

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708783885264

Affiliations: Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA.

Publication date: March 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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