Enhanced post-receptor insulin effects in women following dehydroepiandrosterone infusion.

Abstract

We hypothesized that intravenous dehydroepiandrosterone (DHEA) would decrease insulin resistance in normal and insulin-resistant women. Five insulin-resistant women diagnosed as having polycystic ovaries (PCO) with elevated testosterone and normal dehydroepiandrosterone sulfate (DHEAS) with amenorrhea were recruited. Obese controls (OC) with normal menses and normal testosterone and DHEAS were recruited 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 level of 330 +/- 55 pmol/L, and DHEAS level of 3.4 +/- 1.3 mumol/L. An oral glucose tolerance test (OGTT) was performed at 8 AM after an overnight 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 morning at 8 AM. T-lymphocytes were drawn at 8 AM each morning. The DHEA infusion had no significant effect on any of the in vivo indices of insulin sensitivity, ie, basal and OGTT insulin, C-peptide, and ratios of insulin/glucose. In vitro, DHEA significantly increased insulin binding to T-lymphocytes of PCO women but caused no significant change in OC women. There was, however, marked enhancement of T-lymphocyte pyruvate dehydrogenase (PDH) activities in both groups of study subjects following DHEA. We conclude that a 17-hour infusion of DHEA enhanced T-lymphocyte insulin binding and PDH activity while producing no detectable improvements in in vivo indices of insulin sensitivity.