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

Stuart Morgan, Jeremy Tomlinson

    Research output: Contribution to journalArticle

    44 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)1067-76
    Number of pages10
    JournalExpert opinion on investigational drugs
    Volume19
    Issue number9
    DOIs
    Publication statusPublished - 1 Sep 2010

    Keywords

    • glucocorticoids
    • 11beta-hydroxysteroid dehydrogenase type 1
    • metabolic syndrome
    • obesity
    • 11 beta-HSD1
    • insulin resistance
    • type 2 diabetes

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