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Inhibition of p-enolpyruvate carboxykinase gene expression: role of insulin, phorbol esters and/or calcium ionophore

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7107064
; ; ; ;
Both insulin and phorbol esters are known to inhibit the transcription of the gene for P-enolpyruvate carboxykinase (GTP) (PEPCK). The promoter-regulatory region of the PEPCK gene was analyzed for responsive sequences, using a series of chimeric genes constructed by fusing segments of the 5'-flanking region of the PEPCK gene (containing a graded set of deletions) to the structural gene for Herpes virus thymidine kinase (TK). These chimeric genes were transfected into TK-deficient rat hepatoma cells and their level of expression and regulation by insulin, phorbol ester and calcium ionophore was tested. A segment of the PEPCK promoter-regulatory region spanning 2 kb was shown to be sensitive to regulation by cAMP and glucocorticoids but not to insulin. In these same cells, insulin effectively inhibited the expression of the endogenous PEPCK gene. In a parallel set of experiments, they showed drastic alterations in the expression of the chimeric PEPCK-TK gene when cells were exposed to phorbol ester and/or calcium ionophore. These findings suggest that functional sequences required for insulin regulation of the PEPCK gene expression are 3' to the promoter-regulatory region of the gene.
Research Organization:
Case Western Reserve Univ., Cleveland, OH
OSTI ID:
7107064
Report Number(s):
CONF-8606151-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METAL COMPOUNDS
AMP
ANIMAL CELLS
BIOLOGICAL EFFECTS
CALCIUM COMPOUNDS
CARBON-CARBON LYASES
CARBOXY-LYASES
CARCINOGENS
DISEASES
ENZYMES
ESTERS
GENES
HEPATOMAS
HORMONES
INHIBITION
INSULIN
LYASES
MICROORGANISMS
NEOPLASMS
NUCLEOTIDES
ORGANIC COMPOUNDS
PARASITES
PEPTIDE HORMONES
PHORBOL ESTERS
TRANSCRIPTION
TUMOR CELLS
VIRUSES