11-Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors in type 2 diabetes mellitus and obesity

Expert Opin Investig Drugs. 2008 Apr;17(4):481-96. doi: 10.1517/13543784.17.4.481.

Abstract

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.

Method: 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.

Results/conclusion: 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.

Publication types

  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • Animals
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Glucocorticoids / antagonists & inhibitors
  • Glucocorticoids / metabolism
  • Humans
  • Hydrocortisone / antagonists & inhibitors
  • Hydrocortisone / metabolism
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / enzymology
  • Molecular Structure
  • Obesity / drug therapy*
  • Obesity / enzymology
  • Treatment Outcome

Substances

  • Anti-Obesity Agents
  • Enzyme Inhibitors
  • Glucocorticoids
  • Hypoglycemic Agents
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • HSD11B1 protein, human
  • Hydrocortisone