Dysregulation of Δ 4 -3-oxosteroid 5β-reductase in diabetic patients: Implications and mechanisms
| Autor: | Yuan Chen, Christina Nadolny, Sangmin You, Mwlod Ghareeb, Liangran Guo, Ruitang Deng, Stephanie Shiffka, Ruchi Verma, Leila Valanejad, Fatemeh Akhlaghi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Peroxisome proliferator-activated receptor 030209 endocrinology & metabolism Biology Cholesterol 7 alpha-hydroxylase Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Chenodeoxycholic acid Internal medicine medicine Molecular Biology chemistry.chemical_classification Bile acid Steroid hormone 030104 developmental biology chemistry Homeostasis Steroid hormone metabolism Hormone |
| Zdroj: | Molecular and Cellular Endocrinology. 470:127-141 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2017.10.005 |
| Popis: | Aldo-keto reductase family 1 member D1 (AKR1D1) is a Δ4-3-oxosteroid 5β-reductase required for bile acid synthesis and steroid hormone metabolism. Both bile acids and steroid hormones, especially glucocorticoids, play important roles in regulating body metabolism and energy expenditure. Currently, our understanding on AKR1D1 regulation and its roles in metabolic diseases is limited. We found that AKR1D1 expression was markedly repressed in diabetic patients. Consistent with repressed AKR1D1 expression, hepatic bile acids were significantly reduced in diabetic patients. Mechanistic studies showed that activation of peroxisome proliferator-activated receptor-α (PPARα) transcriptionally down-regulated AKR1D1 expression in vitro in HepG2 cells and in vivo in mice. Consistently, PPARα signaling was enhanced in diabetic patients. In summary, dysregulation of AKR1D1 disrupted bile acid and steroid hormone homeostasis, which may contribute to the pathogenesis of diabetes. Restoring bile acid and steroid hormone homeostasis by modulating AKR1D1 expression may represent a new approach to develop therapies for diabetes. |
| Databáze: | OpenAIRE |
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