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 gl ucose 6-phosphate (G-6-P) transporter gene expression by insulin in conscio us dogs in vivo and in tissue culture cells in situ were compared. In pancr eatic-clamped, euglycemic conscious dogs, a 5-h period of hypoinsulinemia l ed 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 hyperi nsulinemia 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 c ells. However, the magnitude of the insulin effect was much greater on G-6- Pase catalytic subunit gene expression and was manifested more rapidly. Fur thermore, cAMP stimulated G-6-Pase catalytic subunit expression in H4IIE ce lls and in primary hepatocytes but had no effect on G-6-P transporter expre ssion. 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.