To test the hypothesis that insulin acutely enhances the metabolic clearance rate (MCR) of dehydroepiandrosterone in humans, the effect of a short-term insulin infusion on the MCR of dehydroepiandrosterone was assessed in 10 men and 7 women. After an overnight fast, dehydroepiandrosterone was infused at 3.47 jumol/h for 6.5 h. At 240 min, a hyperinsulinemic-euglycemic clamp was begun by infusing insulin at 21.5 pmol/kg per min for 2.5 h. MCR of dehydroepiandrosterone was calculated at baseline (210-240 min) and during the insulin infusion (360-390 min). A control study was conducted at least 1 wk later, in which 0.45% saline was substituted for the hyperinsulinemic-euglycemic clamp. During the insulin clamp study, serum insulin rose from 34±2 to 1084±136 pmol/liter (P = 0.0001) in men and from 40±5 to 1357+175 pmol/liter (P = 0.0003) in women, while serum glucose remained constant in both groups. MCR of dehydroepiandrosterone rose in men during the insulin infusion from 2443±409 to 3599±500 liters/ 24 h (P = 0.003), but did not change during the control saline infusion. In contrast, MCR of dehydroepiandrosterone in women did not change in the insulin clamp study during insulin infusion (2526±495 liters/24 h at baseline vs. 2442±491 liters/24 h during insulin infusion; P = 0.78). These findings suggest that insulin acutely increases the MCR of dehydroepiandrosterone in men but not in women.

These results suggest that insulin increases the DHEA metabolic clearance rate by stimulating its conversion to DHEA-FA and by enhancing uptake of DHEA-FA by peripheral tissues.