title: Selective tonic inhibition of G-6-Pase catalytic subunit, but not G-6-P transporter, gene expression by insulin in vivo.
abstract: The regulation of glucose-6-phosphatase (G-6-Pase) catalytic subunit and glucose 6-phosphate (G-6-P) transporter gene expression by insulin in conscious dogs in vivo and in tissue culture cells in situ were compared. In pancreatic-clamped, euglycemic conscious dogs, a 5-h period of hypoinsulinemia led to a marked increase in hepatic G-6-Pase catalytic subunit mRNA; however, G-6-P transporter mRNA was unchanged. In contrast, a 5-h period of hyperinsulinemia resulted in a suppression of both G-6-Pase catalytic subunit and G-6-P transporter gene expression. Similarly, insulin suppressed G-6-Pase catalytic subunit and G-6-P transporter gene expression in H4IIE hepatoma cells. However, the magnitude of the insulin effect was much greater on G-6-Pase catalytic subunit gene expression and was manifested more rapidly. Furthermore, cAMP stimulated G-6-Pase catalytic subunit expression in H4IIE cells and in primary hepatocytes but had no effect on G-6-P transporter expression. These results suggest that the relative control strengths of the G-6-Pase catalytic subunit and G-6-P transporter in the G-6-Pase reaction are likely to vary depending on the in vivo environment.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Hornbuckle
authors.forename: D S
authors.initials: DS
authors.lastname: Edgerton
authors.forename: J E
authors.initials: JE
authors.lastname: Ayala
authors.forename: C A
authors.initials: CA
authors.lastname: Svitek
authors.forename: J K
authors.initials: JK
authors.lastname: Oeser
authors.forename: D W
authors.initials: DW
authors.lastname: Neal
authors.forename: S
authors.initials: S
authors.lastname: Cardin
authors.forename: A D
authors.initials: AD
authors.lastname: Cherrington
authors.forename: R M
authors.initials: RM
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics*; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D002384:Catalysis; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000235:genetics; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D017920:Antiporters; D001786:Blood Glucose; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C503531:SLC37A4 protein, human; C503532:Slc37a4 protein, mouse; C503533:Slc37a4 protein, rat; C111261:glucose 6-phosphate(transporter); D005952:Glucose-6-Phosphatase; D021984:Cyclophilin A