Distinct hormone stimulation and counteraction by insulin of the expression of the two components of glucose 6-phosphatase in HepG2 cells

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 a cells that whereas insulin (0.01-10 nM) suppressed p36 mRNA, it only reduced p46 mRNA by half at 1 mu M. Cyclic AMP (0.01-100 mu M) 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 mu M insulin. The endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (1-100 nM) increased p36 mRNA by a-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. (C) 2000 Academic Press.