HSD11B1

The protein encoded by HSD11B1 is 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), also known as HSD11B or NADP-dependent 11β-hydroxysteroid dehydrogenase. It catalyzes the conversion of inactive cortisone to active cortisol in liver, adipose tissue, and brain, thereby regulating intracellular glucocorticoid levels. This enzyme integrates with the hypothalamic-pituitary-adrenal (HPA) axis and metabolic signaling pathways, modulating glucose homeostasis and lipid metabolism.
Dysregulation of 11β-HSD1 links to metabolic syndrome, type 2 diabetes, obesity, and age-related cognitive decline. Elevated cortisol from overactive 11β-HSD1 promotes insulin resistance and visceral adiposity. Selective inhibitors (e.g., MK-0736) targeting this enzyme are in clinical development for metabolic disorders, with preclinical data showing improved glucose control and reduced fat mass.