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 cells that whereas insulin (0.01-10 nM) suppressed p36 mRNA, it only reduced p46 mRNA by half at 1 microM. Cyclic AMP (0.01-100 microM) 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 microM insulin. The endoplasmic reticulum Ca2+-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.
Li
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Department of Nutrition and Biochemistry, Centre de Recherche du CHUM, University of Montreal, Quebec, Canada.
van de Werve
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G
D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007328:Insulin; D012333:RNA, Messenger; D019284:Thapsigargin; D003907:Dexamethasone; D000242:Cyclic AMP; D005952:Glucose-6-Phosphatase; D000252:Calcium-Transporting ATPases; D005947:Glucose; D002118:Calcium