Selective tonic inhibition of G-6-Pase catalytic subunit, but not G-6-P transporter, gene expression by insulin in vivo.
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.
Hornbuckle
L A
LA
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
Edgerton
D S
DS
Ayala
J E
JE
Svitek
C A
CA
Oeser
J K
JK
Neal
D W
DW
Cardin
S
S
Cherrington
A D
AD
O'Brien
R M
RM
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
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