Faculty Research 1980 - 1989

Title

Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ-db/db).

Document Type

Article

Publication Date

1984

Keywords

Animal, Blood-Glucose: me, Body-Weight: de, Comparative-Study, Dehydroepiandrosterone: aa, Diabetes-Mellitus-Experimental: dt, Diet, Drug-Synergism, Drug-Therapy-Combination, Estradiol: tu, Insulin, Male, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

JAX Location

46,553

JAX Source

Endocrinology. 1984 Jul; 115(1):239-43.

Grant

AM14461, AM17631, AM27722

Abstract

Dehydroepiandrosterone (DHEA) fed at 0.4% in the diet is known to exert strong antihyperglycemic effects in C57BL/KsJ genetically diabetic (db/db) mice. Three of the major metabolic products of DHEA; DHEA sulfate, alpha-hydroxyetiocholanolone (alpha-ET), and beta-hydroxyetiocholanolone (beta-ET) when fed at 0.1% in the diet, and one putative product, 17 beta-estradiol, when fed at 0.005% also prevented the development of severe diabetes while having little effect on the amount of food eaten or the rate of weight gain. When suboptimal doses (5-20 micrograms/week) of estradiol were injected in combination with diets containing either alpha-ET or beta-ET, marked potentiating effect was noted, normalization of the hyperglycemia being produced with as little as 0.025% of beta-ET and 0.05% of alpha-ET. The ability of the etiocholanolones to maintain islet integrity and prevent the development of most diabetes symptoms suggests that these metabolites are not merely inactive end products of steroid metabolism, but are physiological effectors in their own right.

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