11β-Hydroxysteroid dehydrogenase type 1 inhibitors for metabolic syndrome

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. 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the interconversion of glucocorticoids through the activity of two isozymes: type 1 (11 beta-HSD1) and type 2 (11 beta-HSD2). 11 beta-HSD1 converts inactive glucocorticoid to the active form, whereas 11 beta-HSD2 converts active glucocorticoid to the inactive form. It is well established that reduced 11 beta-HSD2 activity causes hypertension and electrolyte abnormalities. More recently, the pathophysiological role of 11 beta-HSD1 has been explored and studies suggest that increased 11 beta-HSD1 activity within target tissues may promote insulin resistance, obesity, hypertension and dyslipidemia. This review will discuss the evidence that inhibition of 11 beta-HSD1 may be therapeutic in the treatment of the metabolic syndrome.