Role of 11beta-hydroxysteroid Dehydrogenase Inhibitors in Metabolic Syndrome and its Expansion in other Therapeutic Options
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Date
2012
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Sebha University
Abstract
The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to promote the development of diabetes and cardiovascular disease. These risk factors include abdominal obesity, insulin resistance, hypertension and dyslipidemia. 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) catalyzes the interconversion of glucocorticoids through the activity of two isozymes: type 1 (11beta-HSD1) and type 2 (11beta-HSD2). 11beta-HSD1 converts inactive glucocorticoid to the active form, whereas 11beta-HSD2 converts active glucocorticoid to the inactive form. Glucocorticoids play a pivotal role in regulating fat metabolism, function and distribution. Evidence has accumulated that enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which regenerates active glucocorticoids from inactive forms and plays a central role in regulating intracellular glucocorticoid concentration, is commonly elevated in fat depots from obese individuals. . This suggests a role for local glucocorticoid reactivation in obesity and the Metabolic Syndrome. 11beta-HSD1 knockout mice resist visceral fat accumulation and insulin resistance even on a high-fat diet. In summary, 11beta-HSD1 is a promising pharmaceutical target for the treatment of the Metabolic Syndrome. Animal studies and pharmacological experiments suggest further unrelated target areas, for example improvement of cognitive function and treatment of glaucoma, osteoporosis due to the role of glucocorticoids and cellular activation by 11 beta HSD1 in these pathologies.
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Keywords
11 Beta hydroxysteroid dehydrogenase inhibitors, metabolic syndrome, glucocorticoids, obesity, type 2 diabetes.