11beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of type 2 diabetes.

Journal article

IMPORTANCE OF THE FIELD: The prevalence of obesity and type 2 diabetes is rising and reaching pandemic proportions. For this reason, identification of novel therapeutic targets is urgently needed. AREAS COVERED IN THIS REVIEW: The endoluminal enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes glucocorticoid activation in key metabolic tissues including skeletal muscle, liver and adipose tissue, and is strongly implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome. Selective 11beta-HSD1 inhibitors limit local glucocorticoid availability and improve insulin sensitivity, glucose tolerance, lipid profiles and atherosclerosis. To date, there is a paucity of clinical studies using selective 11beta-HSD1 inhibitors; however, early indications show that these compounds have great therapeutic potential. WHAT THE READER WILL GAIN: We present a comprehensive overview of the background to the development of selective 11beta-HSD1 inhibitors, the preclinical data supporting 11beta-HSD1 as a therapeutic target, and the current status of clinical trials of these agents. TAKE HOME MESSAGE: Selective 11beta-HSD1 inhibitors have the potential to improve insulin sensitivity and may ultimately add to the treatment options available for patients with type 2 diabetes. However, further clinical studies are urgently required.

Authors: Morgan, SA; Tomlinson, J

• Publication status: Published
• Journal: Expert opinion on investigational drugs
• Volume: 19
• Issue: 9
• Pages: 1067-1076
• Publication date: 2010-09-01
• DOI: 10.1517/13543784.2010.504713
• EISSN: 1744-7658
• ISSN: 1354-3784
• Language: English
• Keywords: Metabolic Syndrome X; Hypoglycemic Agents; 11-beta-Hydroxysteroid Dehydrogenases; Mice; Adipose Tissue; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Liver; Humans; Obesity; Diabetes Mellitus, Type 2; Lipid Metabolism; Glucocorticoids; Animals; Clinical Trials as Topic; Insulin Resistance