11beta-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. 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. It is well established that reduced 11beta-HSD2 activity causes hypertension and electrolyte abnormalities. More recently, the pathophysiological role of 11beta-HSD1 has been explored and studies suggest that increased 11beta-HSD1 activity within target tissues may promote insulin resistance, obesity, hypertension and dyslipidemia. This review will discuss the evidence that inhibition of 11beta-HSD1 may be therapeutic in the treatment of the metabolic syndrome.
Schnackenberg
Christine G
CG
GlaxoSmithKline Pharmaceuticals, Department of Cardiac Biology, UW2510, Box 1539, 709 Swedeland Road, King of Prussia, PA 19406, USA. Christine.G.Schnackenberg@gsk.com
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000201:enzymology; D009765:Obesity / Q000201:enzymology
D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D005947:Glucose