Starvation or diabetes decreases the content but not the mRNA of 6‐phosphofructo‐2‐kinase in rat liver

Crepin, Karine M.; Darville, Martine I.; Hue, Louis; Rousseau, Guy

doi:10.1016/0014-5793(88)80884-6

Cited by 36 publications

(35 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glucocorticoids stimulate L-type mRNA PFK-2 transcription in rat liver, 8,39,45 whereas glucagon inhibits transcription and destabilizes the L-mRNA. 46 In starved or diabetic rats, refeeding or insulin treatment increases, 17,47,48 whereas starvation causes a decrease in the PFK-2 mRNA levels, both in lean and obese rats. The effects of insulin on L-promoter, depend on the hormonal context.…”

Section: Discussionmentioning

confidence: 99%

Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

et al. 1998

View full text Add to dashboard Cite

OBJECTIVE: To study the mechanism that controls fructose-2,6-bisphosphate (Fru-2,6-P 2 ) accumulation, as well as the mRNAs levels of the glycolyticagluconeogenic regulatory enzymes in the livers of fed and starved lean ( faa-) and obese ( faafa) Zucker rats. DESIGN: Rats were fed a standard chow or deprived of food for 24 h. SUBJECTS: Male lean (faa-) and genetically obese ( faafa) rats (nine weeks old). MEASUREMENTS: Fru-2,6-P 2 concentration, 6-phosphofructo-2-kinase (PFK-2), glucokinase (GK), pyruvate kinase (PK) activities and the mRNA levels of GK, PFK-2, L-type pyruvate kinase, fructose-1,6-bisphosphatase (FBPase-1) and phosphoenolpyruvate carboxykinase (PEPCK) were analyzed. RESULTS: PFK-2aFBPase-2 mRNA decreased during starvation in both faa-and faafa animals. Although PFK2aFBPase-2 mRNA levels were similar in fed lean and obese rats, PFK-2 concentration and activity were higher in fed obese than in fed lean animals, which might explain the high concentration of Fru-2,6-P 2 observed in obese animals. During starvation, PFK-2 protein concentration decreased, correlating with the enzymatic activity and Fru-2,6-P 2 levels. The activities of GK and L-pyruvate kinase (L-PK) also increased in fed obese (faafa) rats compared with fed lean (faa-) animals, but decreased during starvation. The mRNA levels of glycolytic enzymes in fed obese rats were similar (PFK-2) or higher than (GK, L-PK) in fed lean animals. During starvation, they decreased in lean and obese rats with one important exception, GK mRNA remained high in obese animals. The mRNA of gluconeogenic enzymes remained constant (FBPase-1) or increased (PEPCK) during fasting. CONCLUSION: The changes observed might be explained by the hyperinsulinaemia observed in the liver of obese rats, which might lead to the stimulation of glycolysis and lipogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Glucagon inhibits transcription from the L promoter and destabilizes the L mRNA in vivo [51]. In fasted or diabetic rats, refeeding or insulin treatment increases PFK-2/FBPase-2 mRNA concentration in liver after 24-48 h [52][53][54]. Cifuentes et al [49] and Espinet et al [46] [40] identified in liver chromatin five DNAase I-hypersensitive sites, two of which could correspond to other regulatory regions of gene A.…”

Section: Gene Organizationmentioning

confidence: 99%

Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver

Lemaigre¹,

Rousseau²

1994

Biochemical Journal

100

View full text Add to dashboard Cite

“…Expression of the L, but not the M, isozyme of PFK-2/FBPase-2 is controlled by diet and insulin (6,7).…”

mentioning

confidence: 99%

5' flanking sequence and structure of a gene encoding rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Darville¹,

Crepin²,

Hue³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The synthesis and degradation of fructose 2,6-bisphosphate, a ubiquitous stimulator of glycolysis, are catalyzed by 6-phosphofructo-2-kinase (EC 2.7.1.105) and fructose-2,6-bisphosphatase (EC 3.1.3.46), respectively. In liver, these two activities belong to separate domains of the same 470-residue polypeptide. Various mRNAs have been described for this bifunctional enzyme, which is controlled by hormonal and metabolic signals. To understand the origin and regulation of these mRNAs, we have characterized rat genomic clones encoding the liver isozyme, which is regulated by cAMP-dependent protein kinase, and the muscle isozyme, which is not. We describe here a 55-kilobase gene that encodes these isozymes by alternative splicing from two promoters. Each of the putative promoters was sequenced over about 3 kilobases and found to include nucleotide motifs for binding regulatory factors. The two isozymes share the same 13 exons and differ only by the first exon that, in the liver but not in the muscle isozyme, contains the serine phosphorylated by cAMPdependent protein kinase. The gene was assigned to the X chromosome. An analysis ofthe exon limits of6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in relation to its functional domains and to its similarity with other proteins plus its G+C content at the third codon position suggests that this gene originates from several fusion events.Fructose 2,6-bisphosphate is the most potent allosteric stimulator of 6-phosphofructo-1-kinase (EC 2.7.1.11), a key enzyme of glycolysis. The synthesis of fructose 2,6-bisphosphate is catalyzed by 6-phosphofructo-2-kinase (PFK-2; EC 2.7.1.105) and its degradation is catalyzed by fructose-2,6-bisphosphatase (FBPase-2; EC 3.1.3.46). In liver, these two activities belong to separate domains of each subunit (470 amino acids) of the same homodimeric protein. This bifunctional enzyme integrates a number of hormonal and metabolic signals including cAMP. In fibroblasts, PFK-2 activity is stimulated by growth factors, tumor promoters, and tyrosinespecific oncogenic protein kinases (1, 2).Biochemical and immunologic data suggest the existence of distinct PFK-2/FBPase-2 isozymes. Using PFK-2/ FBPase-2 cDNA probes from rat liver (4), we have identified a 2.1-kilobase (kb) mRNA coding for the liver (L) isozyme, a 1.9-kb mRNA coding for the skeletal muscle (M) isozyme, and a 6.8-kb mRNA presumably coding for the heart isozyme (5). The L and M isozymes have a common sequence of438 amino acids and differ only at the N terminus. In the L isozyme, the divergent sequence is 32 residues long and includes the serine (Ser-32) phosphorylated by cAMP-dependent protein kinase. In the M isozyme, the N terminus is 10 residues long and is unrelated to the unique part of the L isozyme. Expression of the L, but not the M, isozyme of PFK-2/FBPase-2 is controlled by diet and insulin (6, 7). This gene is 55 kb long and contains 15 exons, 13 of which are common to the two isozymes. Part of this work has been presented in the form of an abstract (9). MATERIALS...

show abstract

Starvation or diabetes decreases the content but not the mRNA of 6‐phosphofructo‐2‐kinase in rat liver

Cited by 36 publications

References 21 publications

Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver

5' flanking sequence and structure of a gene encoding rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Contact Info

Product

Resources

About