title: Effects of dehydroepiandrosterone on gluconeogenic enzymes and glucose uptake in human hepatoma cell line, HepG2.
abstract: Dehydroepiandrosterone (DHEA), the most abundant human adrenal steroid, improves insulin sensitivity and obesity in human and model animals. In a previous study, we reported that orally administered DHEA suppresses the elevated activities of hepatic gluconeogenic enzymes like glucose-6-phosphatase (G6Pase) in C57BL/KsJ-db/db mice. However, the molecular mechanisms by which DHEA ameliorates insulin resistance are not clearly understood. In the present study, we cultured the human hepatoma cell line HepG2 with DHEA and measured the enzyme activity and protein expression of G6Pase to investigate the direct effect of DHEA on glucose metabolism in hepatocytes. DHEA significantly suppressed both the activity and protein expression of G6Pase. Moreover, DHEA decreased the gene expression of G6Pase and phosphoenolpyruvate carboxykinase, both of which were maximal at 1 microM DHEA, whereas the mRNA level of glucose-6-phosphate translocase was unchanged. Furthermore, DHEA enhanced 2-deoxyglucose uptake, although its effect was much smaller than that of insulin. These results suggest that DHEA may act at multiple steps in the regulation of glucose metabolism in the liver.
authors.affiliation: Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamashita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saito
authors.forename: Shinobu
authors.initials: S
authors.lastname: Satoh
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aoki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kaburagi
authors.forename: Hisahiko
authors.initials: H
authors.lastname: Sekihara
mesh_terms: D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005943:Gluconeogenesis / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D019298:Glucose-6-Phosphate; D003847:Deoxyglucose; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D005952:Glucose-6-Phosphatase; D005947:Glucose