Effect of dehydroepiandrosterone on glucose uptake in cultured human fibroblasts

Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) reportedly have antidiabetic and antiobesity effects. The effect of DHEA on glucose uptake in cultured human fibroblasts was examined. Incubation of cells with supraphysiologic concentrations of DHEA (10^-5 mol/L) for ≥10 hours enhanced 2-deoxyglucose (2-DG) uptake significantly (P < .05). Supraphysiologic concentrations of insulin (10^-7 mol/L) increased the sensitivity of glucose uptake to DHEA. Conversely, the sensitivity of glucose uptake to insulin was increased by incubating cells with 10^-6 mol/L DHEA. Both the abundance of transcripts encoding glucose transporter-1 (Glut-1) and the maximal velocity (Vmax) of 2-DG transport were increased in cultured fibroblasts incubated with DHEA. Cultured fibroblasts expressed a specific binding factor with low affinity for [³H]DHEA (maximal number of binding sites, 18,496 sites per cell; K_d, 298 nmol/L). Other androgen hormones exerted a less-marked effect on glucose uptake; DHEA-S had no effect. These results suggested that DHEA increases Glut-1 mRNA through binding to a specific factor in cultured human fibroblasts and thereby stimulates glucose uptake in these cells.