ArticleScientific reports2016
11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) mediates insulin resistance through JNK activation in adipocytes.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Small Molecule Insulin Sensitisers: New Leads and Targets for Next-Generation Insulin Sensitising Strategies.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Discovery of novel potential 11β-HSD1 inhibitors through combining deep learning, molecular modeling, and bio-evaluation.Molecular diversity · 2025Article
- Scalable and sustainable reductive amidation of nitroarenes, nitroalkenes, and nitroalkyls with acyl saccharins in aqueous media.Communications chemistry · 2025Article
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- Evaluation of the Antidiabetic Activities of the Fruit ofBioinformatics and biology insights · 2024Review
- Discovery of novel inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 usingJournal of diabetes and metabolic disorders · 2023Article
- Weak Noncovalent Interactions in Three Closely Related Adamantane-Linked 1,2,4-TriazoleMolecules (Basel, Switzerland) · 2022Article
- Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions.Nature reviews. Endocrinology · 2022Review
- Calcium-Deficiency during Pregnancy Affects Insulin Resistance in Offspring.International journal of molecular sciences · 2021Review
- Cortisol on Circadian Rhythm and Its Effect on Cardiovascular System.International journal of environmental research and public health · 2021Review
- Molecular Mechanisms of Glucocorticoid-Induced Insulin Resistance.International journal of molecular sciences · 2021Review
- Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress.Cellular and molecular life sciences : CMLS · 2020Review
- Inter-correlations Among Clinical, Metabolic, and Biochemical Parameters and Their Predictive Value in Healthy and Overtrained Male Athletes: The EROS-CORRELATIONS Study.Frontiers in endocrinology · 2019Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoids are used to treat a number of human diseases but often lead to insulin resistance and metabolic syndrome. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Despite the known role of 11β-HSD1 and active glucocorticoid in causing insulin resistance, the molecular mechanisms by which insulin resistance is induced remain elusive. The aim of this study is to identify these mechanisms in high fat diet (HFD) experimental models. Mice on a HFD were treated with 11β-HSD1 inhibitor as well as a JNK inhibitor. We then treated 3T3-L1-derived adipocytes with prednisone, a synthetic glucocorticoid, and cells with 11β-HSD1 overexpression to study insulin resistance. Our results show that 11β-HSD1 and JNK inhibition mitigated insulin resistance in HFD mice. Prednisone stimulation or overexpression of 11β-HSD1 also caused JNK activation in cultured adipocytes. Inhibition of 11β-HSD1 blocked the activation of JNK in adipose tissue of HFD mice as well as in cultured adipocytes. Furthermore, prednisone significantly impaired the insulin signaling pathway, and these effects were reversed by 11β-HSD1 and JNK inhibition. Our study demonstrates that glucocorticoid-induced insulin resistance was dependent on 11β-HSD1, resulting in the critical activation of JNK signaling in adipocytes.
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