Studies on the hormonal regulation of hepatic metabolism
The effects of hormones on glycolysis, glycogenolysis, and the pentose phosphate pathway in freshly isolated rat hepatocytes were studied. Epidermal growth factor (EGF) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulated glycolysis, as measured by lactate production. Both of these agents also increased [sup 3]H[sub 2]O release from [3-[sup 3]H]glucose, a measure of flux through phosphofructo-1-kinase, the key regulatory enzyme of glycolysis. The stimulations of glycolysis were not secondary to stimulation of glycogenolysis, since neither EGF nor TPA affected glucose production by hepatocytes. EGF, but not TPA, produced a small increase in the level of fructose 2,6-bisphosphate, an activator of phosphofructo-1-kinase. Both EGF and TPA produced a small decrease in the level of citrate, an inhibitor of phosphofructo-1-kinase. In addition, both of these agents stimulated flux through the pentose phosphate pathway, as measured by [sup 14]CO[sub 2] production from [1-[sup 14]C]glucose. The similar effects of EGF and TPA suggest that protein kinase C may be a mediator of EGF action in hepatocytes. EGF and vasopressin, a Ca[sup 2+]-mobilizing hormone in liver, stimulated glycolysis in Ca[sup 2+]-depleted cells, in which hormones are unable to mobilize Ca[sup 2+] from internal pools. This suggests that protein kinase C is also involved in the stimulation of glycolysis by vasopressin. The hypothesis that regulation of phospholipase A[sub 2] by specific inhibitory proteins is involved in hormone action was also examined. Several proteins were found to inhibit or stimulate phospholipase A[sub 2] in vitro in a fashion that was entirely dependent upon assay conditions. The nonspecificity of proteins an the variation of effects with assay condition casts doubt on the importance of this mechanism of regulation in cellular signal transduction.
- Research Organization:
- Kansas State Univ., Manhattan, KS (United States)
- OSTI ID:
- 6913224
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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HORMONES
BIOLOGICAL FUNCTIONS
LIVER CELLS
METABOLISM
PHORBOL ESTERS
BIOLOGICAL EFFECTS
CARBON 14
GLYCOGEN
GLYCOLYSIS
GROWTH FACTORS
HYDROLASES
PENTOSES
PHOSPHOTRANSFERASES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOPRESSIN
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOHYDRATES
CARBON ISOTOPES
CARCINOGENS
ENZYMES
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EVEN-EVEN NUCLEI
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MITOGENS
MONOSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
PITUITARY HORMONES
POLYSACCHARIDES
PROTEINS
RADIOISOTOPES
SACCHARIDES
SOMATIC CELLS
TRANSFERASES
YEARS LIVING RADIOISOTOPES
560300* - Chemicals Metabolism & Toxicology