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11β-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1)
- Target
- HSD11B1
- Molecular classification
- Enzyme, Short-chain dehydrogenases/reductases family
01
Overview
11β-Hydroxysteroid dehydrogenase type 1 (HSD11B1) is an NADPH-dependent enzyme that catalyzes the conversion of inactive cortisone to active cortisol. It is highly expressed in the liver, adipose tissue, and central nervous system. By regulating local glucocorticoid action, HSD11B1 plays essential roles in carbohydrate metabolism, adipose tissue function, memory processes, blood vessel reactivity, blood pressure regulation, obesity development and osteoporosis risk. Therapeutic inhibition of HSD11B1 is being explored for treating obesity, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular complications. Deficiency states can result from mutations affecting either HSD11B1 itself or hexose‐6‐phosphate dehydrogenase.
- Other names
- 11-DH11-beta-HSD1CORTRD2HDLHSD11HSD11BHSD11LSDR26C1Cortisone Reductase
02
Mechanism of action
Therapeutic inhibition of HSD11B1 to reduce local cortisol levels in metabolic tissues.
03
Biological functions
Glucocorticoid metabolismCortisone reduction to cortisolRegulation of glucocorticoid receptor (GR) activationRegulation of mineralocorticoid receptor (MR) activationCarbohydrate metabolismHepatic gluconeogenesisAdipose tissue functionMemory processesBlood vessel reactivityBlood pressure regulation
04
Disease associations
ObesityMetabolic syndromeInsulin resistance/type 2 diabetes mellitusCardiovascular complicationsOsteoporosis
05
Safety considerations
Potential for adverse effects related to altered glucocorticoid levels.Cortisone reductase deficiency
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