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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 mumol/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.

Sex-specific action of insulin to acutely increase the metabolic clearance rate of dehydroepiandrosterone in humans.