[Reduction of obesity-related metabolic risk by modulating tissue exposition to cortisol].
The 11-beta-hydroxysteroid dehydrogenase type 1 (11HSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the liver and the adipose tissue. It may play a role in the pathophysiology of abdominal obesity and the metabolic syndrome, both showing some similarities with the Cushing syndrome. Considering experimental results obtained in rodents, the inhibition of this enzyme could exert favourable metabolic effects, with significant reductions in plasma glucose, insulin resistance and dyslipidaemia. Synthetic inhibitors of 11HSD1 are currently in development with encouraging preliminary results, first in animals, and more recently in humans. Selective inhibitors of 11HSD1 may represent an innovative approach in the pharmacological management of obesity, metabolic syndrome and type 2 diabetes in a near future.
Iovino
Alessandra
A
Unité de pharmacologie clinique, Service de diabétologie, nutrition et maladies métaboliques, Département de médecine, CHU Sart Tilman (B35) 4000 Liège, Belgique.
Paquot
Nicolas
N
Scheen
André J
AJ
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000201:enzymology; D009765:Obesity / Q000188:drug therapy* / Q000201:enzymology
D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1