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

Expert Opin Investig Drugs. 2010 Sep;19(9):1067-76. doi: 10.1517/13543784.2010.504713.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • 11-beta-Hydroxysteroid Dehydrogenases / antagonists & inhibitors
  • 11-beta-Hydroxysteroid Dehydrogenases / metabolism
  • Adipose Tissue / enzymology
  • Adipose Tissue / metabolism
  • Animals
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Lipid Metabolism
  • Liver / metabolism
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / enzymology
  • Metabolic Syndrome / metabolism
  • Mice
  • Obesity / enzymology
  • Obesity / metabolism

Substances

  • Glucocorticoids
  • Hypoglycemic Agents
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • 11-beta-Hydroxysteroid Dehydrogenases