ENHANCED POSTRECEPTOR INSULIN EFFECTS IN WOMEN FOLLOWING DEHYDROEPIANDROSTERONE INFUSION

OBJECTIVE: We hypothesized that intravenous dehydroepiandrosterone (DH EA) would decrease insulin resistance in normal and insulin-resistant women. METHODS: Five insulin-resistant women diagnosed as having polyc ystic ovaries (PCO) with elevated testosterone and normal dehydroepian drosterone sulfate (DHEAS) with amenorhea were recruited. Obese contro ls (OC) with normal menses and normal testosterone and DHEAS weve recr uited and matched to each PCO woman for age and weight. The PCO women had a mean testosterone of 3.2 +/- 0.4 nmol/L, fasting serum insulin l evel of 330 +/- 55 pmol/L, and DHEAS level of 3.4 +/- 1.3 mu mol/L. An oral glucose tolerance rest (OGTT) tvas performed at 8 AM after an ov ernight fast. A DHEA infusion (1 mg/hour for 17 hours) was begun at 6 PM and continued until the completion of the second OGTT performed the following mourning at 8 AM. T-lymphocytes were drawn at 8 AM each mor ning. RESULTS: The DHEA infusion had no significant effect on any of t he in vivo indices of insulin sensitivity, ie, basal and OGTT insulin, C-peptide, and ratios of insulin/glucose. In vitro, DHEA significantl y increased insulin binding to T-lymphocytes of PCO women but caused n o significant change in OC women. There was, however, marked enhanceme nt of T-lymphocyte pyruvate dehydrogenase (PDH) activities in both gro ups of study subjects following DHEA. CONCLUSION: We conclude that a 1 7-hour infusion of DHEA enhancement T-lymphocyte insulin binding and P DH activity while producing no detectable improvements in in vivo indi ces of insulin sensitivity.