ArticleAmerican journal of physiology. Endocrinology and metabolism2015
11β-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 43 citations in OpenAlex.
- Human Adipose Tissue 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition Without Tachyphylaxis by Clofutriben, a Pseudo-Irreversible Enzyme Inhibitor.Clinical and translational science · 2025Article
- Adipocyte STAT5 (signal transducer and activator of transcription 5) is not required for glucocorticoid-induced metabolic dysfunction.American journal of physiology. Endocrinology and metabolism · 2023Article
- Novel targets for potential therapeutic use in Diabetes mellitus.Diabetology & metabolic syndrome · 2023Review
- The role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression.Frontiers in endocrinology · 2023Review
- Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism.International journal of molecular sciences · 2021Review
- Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism.Endocrinology · 2021Review
- Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Attenuates High-Fat Diet-Induced Hepatic Steatosis in Mice.Drug design, development and therapy · 2021Article
- Lack of adipose-specific hexose-6-phosphate dehydrogenase causes inactivation of adipose glucocorticoids and improves metabolic phenotype in mice.Clinical science (London, England : 1979) · 2019Article
- Role of Hepatic Glucocorticoid Receptor in Metabolism in Models of 5αR1 Deficiency in Male Mice.Endocrinology · 2019Article
- AKR1D1 regulates glucocorticoid availability and glucocorticoid receptor activation in human hepatoma cells.The Journal of steroid biochemistry and molecular biology · 2019Article
- Ectopic lipid deposition mediates insulin resistance in adipose specific 11β-hydroxysteroid dehydrogenase type 1 transgenic mice.Metabolism: clinical and experimental · 2019Article
- Enhanced hexose-6-phosphate dehydrogenase expression in adipose tissue may contribute to diet-induced visceral adiposity.International journal of obesity (2005) · 2018Article
- Glucocorticoid-Induced Metabolic Disturbances Are Exacerbated in Obese Male Mice.Endocrinology · 2018Article
- Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.Diabetes · 2017Article
- 11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) mediates insulin resistance through JNK activation in adipocytes.Scientific reports · 2016Article
- Increased glycogen synthase kinase-3β and hexose-6-phosphate dehydrogenase expression in adipose tissue may contribute to glucocorticoid-induced mouse visceral adiposity.International journal of obesity (2005) · 2016Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Long-term glucocorticoid exposure increases the risk for developing type 2 diabetes. Prereceptor activation of glucocorticoid availability in target tissue by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic syndrome. We explored whether the tissue-specific modulation of 11β-HSD1 and H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and lipolysis and analyzed the effects of 11β-HSD1 inhibition on the key lipid metabolism genes and insulin-signaling cascade. We observed that corticosterone (CORT) treatment increased expression of 11β-HSD1 and H6PDH and induced lipase HSL and ATGL with suppression of p-Thr(172) AMPK in adipose tissue of C57BL/6J mice. In contrast, CORT induced adipose insulin resistance, as reflected by a marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr(308) Akt/PKB. Furthermore, 11β-HSD1 shRNA attenuated CORT-induced 11β-HSD1 and lipase expression and improved insulin sensitivity with a concomitant stimulation of pThr(308) Akt/PKB and p-Thr(172) AMPK within adipose tissue. Addition of CORT to 3T3-L1 adipocytes enhanced 11β-HSD1 and H6PDH and impaired p-Thr(308) Akt/PKB, leading to lipolysis. Knockdown of 11β-HSD1 by shRNA attenuated CORT-induced lipolysis and reversed CORT-mediated inhibition of pThr(172) AMPK, which was accompanied by a parallel improvement of insulin signaling response in these cells. These findings suggest that elevated adipose 11β-HSD1 expression may contribute to glucocorticoid-induced insulin resistance and adipolysis.
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