We found recently (J. Biol. Chem. 274, 33866–33869, 1999) that the expression of the catalytic subunit (p36) and putative glucose 6-phosphate translocase (p46) of the liver glucose 6-phosphatase system was stimulated by cyclic AMP and glucose and repressed by insulin. We now further show in HepG2 cells that whereas insulin (0.01–10 nM) suppressed p36 mRNA, it only reduced p46 mRNA by half at 1 μM. Cyclic AMP (0.01–100 μM) caused a 2.7-fold increase in p36 mRNA but barely increased p46 mRNA. In contrast, dexamethasone (0.1–100 nM) increased both p36 and p46 mRNA by more than 3-fold. The effects of cyclic AMP and dexamethasone were counteracted by 1 μM insulin. The endoplasmic reticulum Ca 2+ -ATPase inhibitor thapsigargin (1–100 nM) increased p36 mRNA by 2-fold but not p46 mRNA. It thus appears that the hormonal changes which affect p36 alone concur with known modifications in glucose production; those that affect both p36 and p46 are rather consistent with glucose storage.