The adrenocortical steroid, dehydroepiandrosterone, has been shown previously to produce an antidiabetic effect in C57BL/KsJ db/db mice. Preliminary clinical data suggest that this steroid may enhance insulin sensitivity in humans. The therapeutic use of dehydroepiandrosterone may be limited by its androgenic action. In a previous study, high-dose dehydroepiandrosterone therapy to postmenopausal women produced marked elevations in plasma testosterone (9-fold) and dihydrotestosterone (20-fold) levels. We previously developed the synthetic steroid, 16α-fluoro-5-androsten-17-one, which lacks the androgenic action of dehydroepiandrosterone yet has retained other biological activities of the native steroid. In this study, administration of 16α-fluoro-5-androsten-17-one in the diet (0.2 and 0.3%) to male C57BL/KsJ db/db mice markedly reduced plasma glucose levels. In contrast, treatment with dehydroepiandrosterone was effective in reducing plasma glucose levels at the 0.2% dose but had no effect at the 0.3% dose, possibly as a result of the androgenic state induced at the higher dose. Dehydroepiandrosterone treatment also produced a 25-fold elevation in plasma testosterone levels and a significant increase in seminal vesicle weights, whereas treatment with 16α-fluoro-5-androsten-17-one had no apparent effect on the weight of the seminal vesicle glands.
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Original Articles| August 01 1993
Antihyperglycemic Effect of Dehydroepiandrosterone Analogue 16α-Fluoro-5-androsten-17-one in Diabetic Mice
Laura L Pashko;
Address correspondence and reprint requests to Dr. Arthur Schwartz, Fels Institute for Cancer Research and Molecular Biology, Temple University Medical School, 3420 North Broad Street, Philadelphia PA 19140.
Laura L Pashko, Arthur G Schwartz; Antihyperglycemic Effect of Dehydroepiandrosterone Analogue 16α-Fluoro-5-androsten-17-one in Diabetic Mice. Diabetes 1 August 1993; 42 (8): 1105–1108. https://doi.org/10.2337/diab.42.8.1105
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