The Role of 11Beta-Hydroxysteroid Dehydrogenase in Metabolic Disease and Therapeutic Potential of 11Beta-HSD1 Inhibitors
Author: Saiah, Eddine1
Source: Current Medicinal Chemistry, Volume 15, Number 7, March 2008 , pp. 642-649(8)
Publisher: Bentham Science Publishers
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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; glucocorticoid; metabolic syndrome; diabetes; obesity
Document Type: Research article
DOI: 10.2174/092986708783885264
Affiliations: 1: Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA.
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