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Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice.
Abstract
Dehydroepiandrosterone (DHEA), a major adrenal secretory steroid in humans, was therapeutic when fed in a concentration of 0.4% to C57BL/KsJ mice with either non-insulin-dependent or insulin-dependent diabetes. Genetically diabetic (db/db) mice of both sexes develop obesity and a glucose intolerance and hyperglycemia associated with insulin resistance by 2 mo of age, and exhibit beta-cell necrosis and islet atrophy by 4 mo. In contrast, DHEA feeding initiated between 1 and 4 mo of age, while only moderately effective in preventing obesity, did prevent the other pathogenic changes and effected a rapid remission of hyperglycemia, a preservation of beta-cell structure and function, and an increased insulin sensitivity as measured by glucose tolerance tests. DHEA feeding was also therapeutic to normal C57BL/KsJ male mice made diabetic by multiple low doses of streptozotocin (SZ). While DHEA treatments did not block either the direct cytotoxic action of SZ on beta-cells or the development of insulitis, the steroid significantly moderated the severity of the ensuing diabetes (reduced hyperglycemia and water consumption, and increased plasma insulin and numbers of residual, granulated beta-cells.
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“The 70 -95% reduction in the formation of DHEA and DHEA-S by the adrenals during aging results in a dramatic reduction in the formation of androgens and estrogens in peripheral target tissues, which could well be involved in the pathogenesis of age-related diseases such as insulin resistance (307, 308) and obesity (309 -311).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [308]
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Quantitative and reproducible murine model of excisional wound healing
Galiano, R. D., Michaels, V. J., Dobryansky, M., Levine, J. P., & Gurtner, G. C. (2004) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2004.12404.x · Cited by 761
Labrie, F., Luu-The, V., Labrie, C., Bélanger, A., Simard, J., Lin, S.-X., & Pelletier, G. (2003) · Endocrine Reviews · doi:10.1210/er.2001-0031 · Cited by 544
“The 70–95% reduction in the formation of DHEA and DHEA-S by the adrenals during aging results in a dramatic reduction in the formation of androgens and estrogens in peripheral target tissues, which could well be involved in the pathogenesis of age-related diseases such as insulin resistance (307, 308) and obesity (309…”
BackgroundAMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons
Claret, M., Smith, M. A., Batterham, R. L., Selman, C., Choudhury, A. I., Fryer, L. G. D., Clements, M., Al‐Qassab, H., Heffron, H., Xu, A. W., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31516 · Cited by 522
Is dehydroepiandrosterone a hormone?
Labrie, F., Luu-The, V., Bèlanger, A., Lin, S.-X., Simard, J., Pelletier, G., & Labrie, C. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06264 · Cited by 460
“…in the formation of androgens and estrogens in peripheral target tissues, which could well be involved in the pathogenesis of age-related diseases such as insulin resistance (Coleman et al. 1982, Schriock et al. 1988) and obesity (Nestler et al. 1988, MacEwen & Kurzman 1991, Tchernof et al. 1995).”
BackgroundNESTLER, J. E., BARLASCINI, C. O., CLORE, J. N., & BLACKARD, W. G. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-1-57 · Cited by 414
Metadata
- Authors
- Coleman, D. L., Leiter, E. H., & Schwizer, R. W.
- Affiliations
- Jackson Laboratory (US)
- ORCID
- Coleman, D L
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1982-09-01
- Volume
- 31
- Issue
- 9
- Pages
- 830-833
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W1998106197
- Cited by
- 317
- References
- 0
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 7 · 2020: 2 · 2019: 2 · 2018: 4 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 3 · 2012: 8
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- dehydroepiandrosterone, type 2 diabetes, type 1 diabetes, db/db mice, streptozotocin-induced diabetes, insulin resistance, beta-cell function, beta cell necrosis, islet atrophy, hyperglycemia, impaired glucose tolerance, obesity, insulitis, plasma insulin, glucocorticoids
- MeSH terms
- Animals, Blood Glucose, Dehydroepiandrosterone, Diabetes Mellitus, Experimental, Female, Male, Mice, Inbred C57BL, Pancreas, Mice
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