The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice
Open accessAbstract
The enzyme 11β–hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11β-HSD1 has a therapeutic effect in mouse models of metabolic syndrome. Administration of a selective, potent 11β-HSD1 inhibitor lowered body weight, insulin, fasting glucose, triglycerides, and cholesterol in diet-induced obese mice and lowered fasting glucose, insulin, glucagon, triglycerides, and free fatty acids, as well as improved glucose tolerance, in a mouse model of type 2 diabetes. Most importantly, inhibition of 11β-HSD1 slowed plaque progression in a murine model of atherosclerosis, the key clinical sequela of metabolic syndrome. Mice with a targeted deletion of apolipoprotein E exhibited 84% less accumulation of aortic total cholesterol, as well as lower serum cholesterol and triglycerides, when treated with an 11β-HSD1 inhibitor. These data provide the first evidence that pharmacologic inhibition of intracellular GC activation can effectively treat atherosclerosis, the key clinical consequence of metabolic syndrome, in addition to its salutary effect on multiple aspects of the metabolic syndrome itself.
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Cited by
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11β-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action
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The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives
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Metadata
- Authors
- Hermanowski-Vosatka, A., Balkovec, J. M., Cheng, K., Chen, H. Y., Hernandez, M., Koo, G. C., Le Grand, C. B., Li, Z., Metzger, J. M., Mundt, S. S., Noonan, H., Nunes, C. N., Olson, S. H., Pikounis, B., Ren, N., Robertson, N., Schaeffer, J. M., Shah, K., Springer, M. S., Strack, A. M., Strowski, M., Wu, K., Wu, T., Xiao, J., Zhang, B. B., Wright, S. D., & Thieringer, R.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-08-15
- Volume
- 202
- Issue
- 4
- Pages
- 517-527
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2100159933
- Cited by
- 364
- References
- 13
- FWCI
- 24.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Hermanowski-Vosatka, A., Balkovec, J. M., Cheng, K., Chen, H. Y., Hernandez, M., Koo, G. C., Le Grand, C. B., Li, Z., Metzger, J. M., Mundt, S. S., Noonan, H., Nunes, C. N., Olson, S. H., Pikounis, B., Ren, N., Robertson, N., Schaeffer, J. M., Shah, K., Springer, M. S., . . . Thieringer, R. (2005). 11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20050119
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
