Impaired suppression of gluconeogenesis induced by overexpression of a noninsulin-responsive phosphoenolpyruvate carboxykinase gene
| Autor: | Joseph Proietto, S.J. Kaczmarczyk, Sofianos Andrikopoulos, G. Rosella, Jeffrey D Zajac |
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| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Carboxy-lyases Recombinant Fusion Proteins medicine.medical_treatment Molecular Sequence Data Glucosephosphate Dehydrogenase Biology Liver Neoplasms Experimental Endocrinology Internal medicine Pyruvic Acid Gene expression Tumor Cells Cultured medicine Animals Insulin RNA Messenger Promoter Regions Genetic Pyruvates Molecular Biology Base Sequence Gluconeogenesis General Medicine Metabolism Enzyme assay Fructose-Bisphosphatase Rats Cell culture Enzyme Induction biology.protein Phosphoenolpyruvate Carboxykinase (GTP) Phosphoenolpyruvate carboxykinase |
| Zdroj: | Molecular Endocrinology. 7:1456-1462 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Despite detailed knowledge of the regulation of individual steps in the gluconeogenic pathway, the relative importance of each step to the overall control of gluconeogenesis by insulin is not known. The aim of this study was to determine the role of phosphoenolpyruvate carboxykinase (PEPCK) in the regulation of gluconeogenesis by insulin. Clones of the rat hepatoma cell line H4IIE-C3 were produced, overexpressing a PEPCK gene, driven by a promoter not responsive to insulin. In these cells basal gluconeogenesis from 2-[14C]pyruvate was increased 2.1-fold compared to controls (4.63 +/- 0.49 nmol/10(5) cells vs. 2.21 +/- 0.24 nmol/10(5) cells after 3 h, P0.05, n = 5). Increased gluconeogenesis was associated with an increase in basal PEPCK mRNA levels (1.9-fold) and enzyme activity (2.8-fold). Insulin (10(-7) M) suppressed basal gluconeogenesis, PEPCK mRNA levels, and enzyme activity in control cells, but no detectable decrease was observed in PEPCK-transfected cells. These experiments provide direct evidence in intact cells that PEPCK is the rate-limiting enzyme in gluconeogenesis from pyruvate and show that insulin's action to inhibit gluconeogenesis is predominantly on the inhibition of PEPCK transcription. |
| Databáze: | OpenAIRE |
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