Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.9 (
glucose-6-phosphatase
)
3,081
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Transcription of the gene encoding the catalytic subunit of
glucose-6-phosphatase
(
G6Pase
) is stimulated by glucocorticoids and strongly repressed by insulin. We have explored the signaling pathways by which insulin mediates the repression of
G6Pase
transcription in H4IIE cells.
Wortmannin
, a phosphatidylinositide 3-kinase (PtdIns 3-kinase) inhibitor blocked the repression of
G6Pase
mRNA expression by insulin. However, both rapamycin, which inhibits p70S6 kinase activation, and PD98059, an inhibitor of mitogen-activated protein kinase activation, were without effect. Insulin inhibited dexamethasone-induced luciferase expression from a transiently transfected plasmid that places the luciferase gene under the control of the
G6Pase
promoter. This effect of insulin was mimicked by the overexpression of a constitutively active PtdIns 3-kinase but not by a constitutively active protein kinase B. Taken together, these data demonstrate that PtdIns 3-kinase activation is both necessary and at least partly sufficient for the repression of
G6Pase
expression by insulin, but neither mitogen-activated protein kinase nor p70S6 kinase are involved. In addition, activation of protein kinase B alone is not sufficient for repression of the
G6Pase
gene. These results imply the existence of a novel signaling pathway downstream of PtdIns 3 kinase that is involved in the regulation of
G6Pase
expression by insulin.
...
PMID:Central role for phosphatidylinositide 3-kinase in the repression of glucose-6-phosphatase gene transcription by insulin. 968 58
