11-Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors in type 2 diabetes mellitus and obesity.
BACKGROUND
Glucocorticoids such as cortisol are important regulators of fuel metabolism during starvation and stress. Chronic glucocorticoid excess induces obesity with multiple features of the metabolic syndrome.


OBJECTIVE
In this article, we review the importance of glucocorticoids in metabolic syndrome and the approaches that have been explored to reduce glucocorticoid action as the basis for novel therapy of Type 2 diabetes and obesity.


METHODS
We focus on the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies glucocorticoid concentrations in key metabolic tissues including liver and adipose tissue.


CONCLUSIONS
Several 11beta-HSD1 inhibitors are in late preclinical or early clinical development and we review here the properties of the class leaders and their potential as the next generation of drugs with multiple benefits in metabolic syndrome.
Hughes
Katherine A
KA
Clinical Fellow University of Edinburgh, Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Webster
Scott P
SP
Walker
Brian R
BR
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000201:enzymology; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy* / Q000201:enzymology; D016896:Treatment Outcome
D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D006854:Hydrocortisone