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 > or = 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; Kd, 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.
Nakashima
N
N
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Haji
M
M
Sakai
Y
Y
Ono
Y
Y
Umeda
F
F
Nawata
H
H
D000328:Adult; D001665:Binding Sites; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006801:Humans; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003847:Deoxyglucose; D005947:Glucose