[Modulation of tissue exposure to cortisol, new perspective for reducing the metabolic risk associated with obesity].
Pharmaceutical research is looking for new alternatives to manage the metabolic disorders associated with obesity. In this context, 11beta hydroxysteroid dehydrogenase type 1 (11HSD1) represents an interesting target. Indeed, this enzyme activates the transformation of inactive cortisone into active cortisol in various tissues. Therefore, it may be responsible for a local hypercortisolism, in adipose tissue and/or liver, which may be implicated in the pathogenesis of abdominal obesity, metabolic syndrome and type 2 diabetes. Thus, the inhibition of 11HSD1 may represent a potential pharmacological target and an innovative therapeutic goal. Several studies in both animals and humans led to the development of specific 11HSD1 inhibitors, with promising preliminary results. Indeed, a reduction in insulin resistance and significant improvements in carbohydrate and lipid profiles have been reported. The present article describes the rationale that led to the development of specific 11HSD1 inhibitors and briefly reports the first results obtained with these molecules, which may become a new class of antidiabetic agents in the future.
Iovino
A
A
Université de Liège.
Scheen
A J
AJ
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003348:Cortisone / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D019317:Evidence-Based Medicine; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000188:drug therapy; D009765:Obesity / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D056128:Obesity, Abdominal / Q000188:drug therapy; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone; D006854:Hydrocortisone