Antihyperglycemic effect of dehydroepiandrosterone analogue 16 alpha-fluoro-5-androsten-17-one in diabetic mice.

Abstract:

: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, 16 alpha-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 16 alpha-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 16 alpha-fluoro-5-androsten-17-one had no apparent effect on the weight of the seminal vesicle glands.

journal_name

Diabetes

journal_title

Diabetes

authors

Pashko LL,Schwartz AG

doi

10.2337/diab.42.8.1105

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

1105-8

issue

8

eissn

0012-1797

issn

1939-327X

journal_volume

42

pub_type

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