11β-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes

Abstract

Obesity and Type 2 diabetes mellitus are associated with abnormal regulation of glucocorticoid metabolism that are highlighted by clinical similarities between the sequelae of insulin resistance and Cushing's syndrome, as well as glucocorticoids' functional antagonism to insulin, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates functionally inert glucocorticoid precursors (cortisone) to active glucocorticoids (cortisol) within insulin target tissues, such as adipose tissue, thereby regulating local glucocorticoid action. Recent data, mainly from rodents, provide considerable evidence for a causal role of 11β-HSD1 for the development of visceral obesity and Type 2 diabetes though data in humans are not unequivocal. This review summarizes current evidence on a possible role of 11β-HSD1 for development of the metabolic syndrome, raising the possibility of novel therapeutic options for the treatment of Type 2 diabetes by inhibition or down-regulation of 11β-HSD1 activity.