Biomaterial Database

Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate. 1997

D Argaud, and T L Kirby, and C B Newgard, and A J Lange

Department of Biochemistry, Medical School, University of Minnesota, Minneapolis, Minnesota 55455-0347, USA.

Glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood glucose concentration, catalyzes the terminal step in gluconeogenesis and glycogenolysis. Glucose, the product of the glucose-6-phosphatase reaction, dramatically increases the level of glucose-6-phosphatase mRNA transcripts in primary hepatocytes (20-fold), and the maximum response is obtained at a glucose concentration as low as 11 mM. Glucose specifically increases glucose-6-phosphatase mRNA and L-type pyruvate kinase mRNA. In the rat hepatoma-derived cell line, Fao, glucose increases the glucose-6-phosphatase mRNA only modestly (3-fold). In the presence of high glucose concentrations, overexpression of glucokinase in Fao cells via recombinant adenovirus vectors increases lactate production to the level found in primary hepatocytes and increases glucose-6-phosphatase gene expression by 21-fold. Similar overexpression of hexokinase I in Fao cells with high levels of glucose does not increase lactate production nor does it change the response of glucose-6-phosphatase mRNA to glucose. Glucokinase overexpression in Fao cells blunts the previously reported inhibitory effect of insulin on glucose-6-phosphatase gene expression in these cells. Raising the cellular concentration of fructose-2,6-bisphosphate, a potent effector of the direction of carbon flux through the gluconeogenic and glycolytic pathways, also stimulated glucose-6-phosphatase gene expression in Fao cells. Increasing the fructose-2,6-bisphosphate concentration over a 15-fold range (12 +/- 1 to 187 +/- 17 pmol/plate) via an adenoviral vector overexpression system, led to a 6-fold increase (0.32 +/- 0. 03 to 2.2 +/- 0.33 arbitrary units of mRNA) in glucose-6-phosphatase gene expression with a concomitant increase in glycolysis and a decrease in gluconeogenesis. Also, the effects of fructose-2, 6-bisphosphate concentrations on fructose-1,6-bisphosphatase gene expression were stimulatory, leading to a 5-6-fold increase in mRNA level over a 15-fold range in fructose-2,6-bisphosphate level. Liver pyruvate kinase and phosphoenolpyruvate carboxykinase mRNA were unchanged by the manipulation of fructose-2,6-bisphosphate level.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D005635	Fructosediphosphates	Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.
D005941	Glucokinase	A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms, and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2.
D005947	Glucose	A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.	Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D005952	Glucose-6-Phosphatase	An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.	Glucosephosphatase,Glucose 6-Phosphatase,Glucose-6-Phosphate Phosphohydrolase,Glucose 6 Phosphatase
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015971	Gene Expression Regulation, Enzymologic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.	Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic