Biomedical subjects

B Bois-Joyeux

Publications and source records attributed to B Bois-Joyeux.

At least 19 recordsLinked to original sources

PubMed2000

Modulation of the far-upstream enhancer of the rat alpha-fetoprotein gene by members of the ROR alpha, Rev-erb alpha, and Rev-erb beta groups of monomeric orphan nuclear receptors.

Expression of the oncodevelopmental alpha-fetoprotein (AFP) gene is tightly regulated and occurs in the yolk sac, fetal liver and intestine, and cancerous liver cells. Transcription of the AFP gene is under the control of three enhancers that are very tissue specific. We have shown that the most upstream of these enhancers, located at -6 kb, works through the combined action of liver-enriched factors and nuclear receptors that bind to three regions of this DNA regulatory element. This study showed that orphan nuclear receptors of the ROR alpha, Re-verb alpha, and Rev-erb beta groups can bind as monomers with high affinity and specificity to an evolutionarily conserved AGGTCA motif in the functionally important region 1 of this AFP enhancer. Transient transfection experiments performed with human HepG2 hepatoma cells showed that overproduction of ROR alpha 4 stimulated the activity of the AFP enhancer in a dose-dependent manner, while that of Rev-erb alpha and Rev-erb beta had the opposite effect. These effects were highly specific and required the integrity of the AGGTCA motif. The action of these nuclear receptors also occurred in the context of the entire 7-kb regulatory region of the rat AFP gene. These results suggest that altering the amounts or activities of these orphan receptors in cells of hepatic or endodermal origin could modulate AFP gene expression in response to a variety of developmental or carcinogenic stimuli.

Animals↗

PubMed1998

Phorbol esters down-regulate alpha-fetoprotein gene expression without affecting growth in fetal hepatocytes in primary culture.

The effects of phorbol esters (phorbol-12,13-dibutyrate, PDB) on alpha-fetoprotein expression and cell growth were assayed by using fetal hepatocytes in primary culture. PDB acts synergistically with epidermal growth factor (EGF) to specifically decrease alpha-fetoprotein (AFP) mRNA levels, without affecting the expression of other genes of the same family, such as albumin and Vitamin D-binding protein (DBP). This effect is PDB-dose dependent, maximal effects being at 10 ng/ml. The implication of protein kinase C (PKC) in this effect seems clear since bisindolylmaleimide (BIS), a specific PKC inhibitor, completely blocks the PDB effect on AFP expression. Nuclear run-on experiments show that the decrease in AFP mRNA levels is mainly due to an inhibition in the transcription rate of the gene. Determination of PKC activities shows that fetal hepatocytes contain mainly Ca(2+)-independent isoenzymes, which patterns of activation was not modified by EGF plus PDB treatment with respect to PDB treatment. We have found that MAPK and JNK activities, c-jun and c-fos mRNA levels and AP-1 binding activity are notably increased when cells are incubated with both EGF and PDB, PDB does not stimulate growth of fetal hepatocytes, measured either as [3H]-thymidine incorporation into DNA or by cell cycle analysis using flow cytometry. All these results suggest that activation of PKC may affect liver gene expression rather than cell growth in fetal hepatocytes.

Albumins↗

PubMed1998

Rat yolk sac explants as a system for studying the regulation of endodermal genes: down-regulation of the alpha-fetoprotein gene by dexamethasone and phorbol ester.

The visceral yolk sac is a fetal membrane with essential placental functions. It is the major site of synthesis of alpha-fetoprotein (AFP), the most abundant plasma protein in the fetus. We developed a system of rat yolk sac explants in serum-free culture medium to study the regulation of endodermal gene expression in yolk sac. The explanted yolk sac tissues retained their double-sided morphology for up to 48 hours. The epithelial cells of both layers remained tightly joined on a basement membrane as seen by light and electron microscopy. This probably accounts for the continued expression of several endodermal cell-specific markers. The levels of mRNA encoding AFP, vitamin D-binding protein (DBP), hepatocyte nuclear factor 1alpha and beta transcription factors did not change during the 48-hour culture period. This reflects the stability of the differentiation state of the yolk sac endodermal cells. Dexamethasone and phorbol ester (TPA) specifically reduced the AFP mRNA level without affecting that of DBP. This suggests that these transduction pathways are functional in the yolk sac during this period of gestation and could be involved in the physiological down-regulation of AFP gene expression before birth. All these results show that this serum-free culture of rat yolk sac explants is a valuable system for further investigating the action of natural compounds and pharmacological drugs on endodermal gene expression during the embryonic and fetal periods.

Animals↗

PubMed1996

Chicken ovalbumin upstream promoter-transcription factor, hepatocyte nuclear factor 3, and CCAAT/enhancer binding protein control the far-upstream enhancer of the rat alpha-fetoprotein gene.

We have further characterized the most distal of the three alpha-fetoprotein (AFP) enhancers required for expression of the AFP gene in fetal hepatocytes and yolk sac endodermal cells. Almost total rat AFP enhancer 3 (E3) activity is driven by a 160-bp fragment at -6 kb containing three target regions for nuclear proteins that cooperate to stimulate transcription from the AFP and the thymidine kinase promoters in HepG2 hepatoma cells. Region 1, recently shown to be crucial for correct function of the enhancer in liver of transgenic mice, is recognized by two sets of transcription factors that bind to partly overlapping sites, 1a and 1b, in a noncooperative and nonexclusive manner. Site 1a contains a motif, AGGTCA, which is recognized by chicken ovalbumin upstream promoter transcription factors (COUP-TFs), but not by hepatocyte nuclear factor 4. Hepatocyte nuclear factor 3 (HNF3) and CCAAT/enhancer binding protein (C/EBP), which bind to regions 2 and 3, respectively, are likely responsible for the liver-specific E3 action. They play a key role by acting in synergy. The participation of nuclear receptors such as COUP-TFs, with C/EBP and HNF3, in the tight control of the distal AFP enhancer is a new, and perhaps key, step toward understanding the regulation and function of this enhancer, which may remain active throughout development.

Animals↗

PubMed1995

The c-jun proto-oncogene down-regulates the rat alpha-fetoprotein promoter in HepG2 hepatoma cells without binding to DNA.

The effects of a phorbol ester (TPA) and of members of the Jun and Fos oncoprotein family on the activity of the rat alpha-fetoprotein (AFP) promoter were checked by using transient expression experiments in HepG2 hepatoma cells. TPA blocked the activity of the rat AFP promoter in a dose-dependent manner. Overexpression of c-Jun specifically repressed the rat AFP promoter but not the albumin promoter. JunB and JunD were poorer inhibitors. c-Fos expression did not potentiate the negative effect of Jun. The Jun-induced repression does not require binding of c-Jun to the AFP promoter. DNase 1 footprinting experiments did not display any high affinity binding site for Jun on the AFP promoter. Integrity of the c-Jun DNA binding domain is not required for the c-Jun protein to block the AFP promoter. The N-terminal part of Jun, which contains the activating domain, is responsible for the repression as shown by using Jun-Gal4 chimera. Jun likely exerts its negative control on the AFP promoter via protein-protein interactions with a not yet identified trans-activating factor within the -134 to +6 region or with a component of the general machinery of transcription. Jun proteins can thus be key intermediates in regulatory cascades which result in the differential modulation of the AFP and albumin gene expression in the course of liver development and carcinogenesis.

Animals↗

PubMed1995

[Several transcription factors participate in the functioning of the alpha-fetoprotein gene promoter].

The oncodevelopmentally regulated alpha-fetoprotein (AFP) gene offers a very good model system to better understand the molecular mechanisms which dictate the specificity of gene expression in liver and control its tight modulation in the course of development and carcinogenesis. Transcription factors of the CCAAT/enhance-binding protein (C/EBP), hepatocyte nuclear factor-1 (HNF-1), and nuclear factor-1 (NF-1) families can bind in vitro to the promoter of the rat AFP gene, which makes the expression of the AFP gene specific to the liver. We have evaluated the influence of some of these factors on the activity of the AFP promoter by transfection of HepG2 hepatoma cells with the appropriate expression vector plus a CAT plasmid under the control of the AFP promoter. A similar plasmid bearing the rat albumin promoter was used as a control. C/EBP alpha, and C/EBP beta acted as transactivators on the AFP promoter, while LIP, a truncated form of C/EBP beta, was a potent negative regulator of the promoter. Interestingly, HNF-1 beta was found to be more potent than HNF-1 alpha in activating the AFP promoter in the HepG2 cells. This effect was highly promoter and cell specific since it did not occur with the rat albumin promoter or in Chinese hamster ovary cells. HNF-1 beta, which is produced earlier than HNF-1 alpha during liver development, would thus have the greater influence on the AFP promoter in early development. Our results pointed to a key role that NF1 might play in the functioning of the AFP promoter. Indeed, overexpression of NF1 induced a specific decrease in the activity of the AFP promoter. Competition between NF1 and HNF-1 for binding to their overlapping binding sites on the AFP promoter would be critical for modulating its activity.

Animals↗

PubMed1994

Members of the CAAT/enhancer-binding protein, hepatocyte nuclear factor-1 and nuclear factor-1 families can differentially modulate the activities of the rat alpha-fetoprotein promoter and enhancer.

The promoter of the rat alpha-fetoprotein (AFP) gene, which makes the expression of the developmentally regulated AFP gene specific to the liver, is a putative target for transcription factors of the CAAT/enhancer-binding protein (C/EBP), hepatocyte nuclear factor-1 (HNF-1) and nuclear factor-1 (NF-1) families. We have evaluated the influence of these factors on the activity of the AFP promoter by transfection of HepG2 hepatoma cells with the appropriate expression vector plus a CAT plasmid under the control of the AFP promoter. A similar plasmid bearing the rat albumin promoter was used as a control. C/EBP alpha, C/EBP beta and D-binding protein (DBP) acted as trans-activators on the AFP promoter, whereas liver inhibitory protein (LIP), a truncated form of C/EBP beta, was a potent negative regulator of the promoter. C/EBP alpha also bound to and stimulated the activity of the AFP enhancer at -2.5 kb. Interestingly, HNF-1 beta was found to be more potent than HNF-1 alpha in activating the AFP promoter. This effect was specific, as it did not occur with the rat albumin promoter. HNF-1 beta, which is produced earlier than HNF-1 alpha during liver development, would thus have the greater influence on the AFP promoter in early development. Both HNF-1s allowed expression of the AFP promoter in cells of nonhepatic origin. Overexpression of NF-1 induced a specific decrease in the activity of the AFP promoter. This strongly suggests that competition between NF-1 and HNF-1 for binding to their overlapping binding sites on the AFP promoter is critical for modulating its activity. Thus changing combinations of these trans-acting factors may tightly modulate the AFP promoter activity in the course of liver development and carcinogenesis.

Animals↗

PubMed1992

Metabolic changes during early starvation in rats fed a low-protein diet in the postweaning growth period.

Metabolic changes during the first 24 hours of starvation were studied in rats previously adapted for 3 weeks during the postweaning growth period to a low-protein diet using lactalbumin as a dietary protein source. Previous adaptation to a high-quality, low-protein diet reduced the effects of early starvation on the loss of body and liver weight. In rats fed a low-protein diet (6% lactalbumin, LP rats), free triiodothyronine (T3) concentration remained higher than in control rats (13% lactalbumin, C rats) throughout the experiment (+38%, 24 hours), and the plasma insulin concentration, which was lower than in C rats during the first 6 hours (-56%), was not different thereafter. Plasma insulin to glucagon molar ratio was lower (-54%) and liver cyclic adenosine monophosphate (cAMP) concentration was higher (+28%) in LP than in C rats in the fed state, but these were not different at 24 hours of starvation. Plasma glucose concentration was slightly lower in LP than in C rats (-15%) in the fed state, but it was not different in both groups during starvation. Whereas they were unchanged in the fed state, plasma lactate concentration was lower (-57%) and free fatty acid and total ketone body concentrations were higher (+38% and +183%, respectively) in LP than in C rats at 24 hours of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Metabolic effects in rats of a diet with a moderate level of medium-chain triglycerides.

Energy intake, weight gain, carcass composition, plasma fuels, hepatic metabolites and lipogenic enzyme activities were studied in adult rats fed either a low fat, high carbohydrate (LF) diet or one of two fat-containing diets in which 32% of the metabolizable energy was constituted by long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Compared with the LF diet, the MCT diet did not depress food and energy intake, weight gain, energy and nitrogen retention or lipid deposition and did not produce ketogenesis. The weight gain of rats fed LCT was 25% higher, and increased lipid deposition was observed. Lower lipogenic enzyme activities were observed in rats fed the LF diet containing 4% corn oil than in rats fed the MCT diet containing 1% corn oil. This effect disappeared when rats previously adapted to the LCT diet were fed LF or MCT diets containing 1% corn oil for 21 d. By d 21, in both groups, hepatic malic enzyme, ATP-citrate lyase, acetyl CoA carboxylase and fatty acid synthase activities were 2.2-, 2.0-, 2.3- and 1.8-fold higher than those of rats fed LCT. Intermediate hepatic glucose-6-phosphate dehydrogenase activities were observed in rats fed the MCT diet, compared with LCT (40% lower) and LF (1.6-fold higher) diets. These data show that in rats fed a diet in which MCT supplies 32% of metabolizable energy, a high activity of lipogenic enzymes is observed, suggesting that MCT had no inhibitory effect on the activity of these enzymes.

Animals↗

PubMed1990

Metabolic changes in rats fed a low protein diet during post-weaning growth.

Metabolic changes in rats fed a low protein diet were investigated during 3 weeks after weaning using lactalbumin (LP) as dietary protein source. The energy intake was higher and the weight gain lower in rats fed the low protein diet (6%, LP group) than in control rats (13% lactalbumin, C group). Low protein diet induced no changes in plasma glucose, free fatty acids, or triacylglycerol concentrations; however, plasma protein and urea concentrations were lower in LP than in C rats. Plasma free T3 was higher in LP than in C rats (+38%, day 21) and insulin progressively decreased during the experimental period (-56%, day 21) without change in glucagon. Liver glycogen and triacylglycerol concentrations (+40% and +180%, respectively, day 21), and cytosolic and mitochondrial redox states increased (+100% and +100%, day 21), and protein concentration was decreased (-15%, day 21). Pyruvate kinase (PK) and malic enzyme activities were higher in LP than in C rats throughout the experiment (+80% and +210%, respectively, day 21), and glucose-6-phosphate dehydrogenase (G6PDH) activity progressively decreased (-65%, day 21). Phosphoenolpyruvate carboxykinase (PEPCK) activity increased after 2 weeks on a LP diet (+35%, day 21) and fatty acid synthetase (FAS) activity increased only during the first week on the diet (+100%, day 7). Such hormonal and metabolic changes appeared to be associated with the development of a futile energy-wasting cycle between pyruvate and phosphoenolpyruvate.

Animals↗

PubMed1990

Age-dependent glycolysis and gluconeogenesis enzyme activities in starved-refed rats.

Food intake, plasma glucose, insulin (I) and glucagon (G), hepatic glycogen and fructose 2,6-bisphosphate (F-2, 6-P2) and liver glucokinase, glucose 6-phosphatase (G6-Pase), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6-PF-2 kinase/F-2, 6-P2ase), pyruvate kinase (PK-L) and phosphoenolpyruvate carboxykinase (PEPCK) activities were measured in 2 and 22-month-old rats before 3 d starvation and after 2, 4, 6, 24 and 48 h refeeding a high carbohydrate (HC, 74% w/w) diet. Expressed per 100 g of body weight, the food intake of old rats was 55% lower than that of young rats and the amount of carbohydrate absorbed hourly during the first 6 h of refeeding was 2.4-fold higher in young than in old rats. During the first 6 h of refeeding plasma glucose increased 2-fold and returned to normal values after 24 h in young rats, while plasma glucose did not change during refeeding in old rats. In young rats [I] fell by 85% after starvation and returned to normal values 2 h after refeeding. [I] was higher in old than in young rats; it decreased by 40% after starvation and returned to the basal value 4 h after refeeding. No marked changes were observed in plasma [G] in both groups. No difference was observed in hepatic glycogen in the two groups, while F-2, 6-P2 was higher in old than in young rats. In young rats, the opposite changes in liver glucokinase and G6-Pase activities occurring after starvation and during refeeding were

Aging↗

PubMed1989

Effects of long-term feeding of high-protein or high-fat diets on the response to exercise in the rat.

The aim of this work was to find by which mechanisms an increased availability of plasma free fatty acids (FFA) reduced carbohydrate utilization during exercise. Rats were fed high-protein medium-chain triglycerides (MCT), high-protein long-chain triglycerides (LCT), carbohydrate (CHO) or high-protein low-fat (HP) diets for 5 weeks, and liver and muscle glycogen, gluconeogenesis and FFA oxidation were studied in rested and trained runner rats. In the rested state the hepatic glycogen store was decreased by fat and protein feeding, whereas soleus muscle glycogen concentration was only affected by high-protein diets. The percentage decrease in liver and muscle glycogen stores, after running, was similar in fat-fed, high-protein and CHO-fed rats. The fact that plasma glucose did not drastically change during exercise could be explained by a stimulation of hepatic gluconeogenesis: the activity of phosphoenolpyruvate carboxykinase (PEPCK) and liver phosphoenolpyruvate (PEP) concentration increased as well as cyclic adenosine monophosphate (AMPc) while liver fructose 2,6-bisphosphate decreased and plasma FFA rose. In contrast, the stimulation of gluconeogenesis in rested HP-, MCT- and LCT-fed rats appears to be independent of cyclic AMP.

Animals↗

PubMed1989

Post-exercise glycogen resynthesis in trained high-protein or high-fat-fed rats after glucose feeding.

This study examined the effect on glycogen resynthesis during recovery from exercise of feeding glucose orally to physically trained rats which had been fed for 5 weeks on high-protein low fat (HP), high-protein/long-chain triglyceride (LCT) or high carbohydrate (CHO) diets. Muscle glycogen remained low and hepatic gluconeogenesis was stimulated by long-term fat or high-protein diets. The trained rats received, via a stomach tube, 3 ml of a 34% glucose solution immediately after exercise (2 h at 20 m.min-1), followed by 1-ml portions at hourly intervals until the end of the experiments. When fed glucose soleus muscle glycogen overcompensation occurred rapidly in the rats fed all three diets following prolonged exercise. In LCT- and CHO-fed rats, glucose feeding appeared more effective for soleus muscle repletion than in HP-fed rats. The liver demonstrated no appreciable glycogen overcompensation. A complete restoration of liver glycogen occurred within a 2- to 4-h recovery period in the rats fed HP-diet, while the liver glycogen store had been restored by only 67% in CHO-fed rats and 84% in LCT-fed rats within a 6-h recovery period. This coincides with low gluconeogenesis efficiency in these animals.

Animals↗

PubMed1988

[Long-term consumption of a diet with moderate medium chain triglyceride content does not inhibit the activity of enzymes involved in hepatic lipogenesis in the rat].

The activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40), ATP-citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthetase were lower (-25 to -60%) in liver of rats fed during 45 days with a moderate long-chain triglycerides (LCT) content diet (32% of metabolizable energy, ME), than in control rats fed with a low fat diet (LCT, 10% of ME). However, the fall in malic enzyme activity was not significant. In contrast, these activities were higher (+40 to +160%) in rats fed with a diet with a moderate medium-chain triglycerides (MCT) content (32% of ME), than in control rats. Nevertheless, the increase in activity of malic enzyme and ATP-citrate lyase was more important. Contrary to LCTs, MCTs had no inhibitory effect on the activity of enzymes involved in hepatic lipogenesis.

ATP Citrate (pro-S)-Lyase↗

PubMed1987

Metabolic effects induced by long-term feeding of medium-chain triglycerides in the rat.

Energy intake, weight gain, carcass composition, plasma hormones and fuels, hepatic metabolites and the activities of phosphoenolpyruvate carboxykinase (PEPCK), malic enzyme, and glucose 6-phosphate dehydrogenase (G6P-DH) were examined in adult rats during a 44-day period of low fat, high carbohydrate (LF) feeding or of consumption of one or two high (70% metabolizable energy) fat diets composed of 63% (metabolizable energy) long-chain (LCT) or medium-chain (MCT) triglycerides. Energy intake was similar in the LCT and MCT groups but was less than that of LF group. The weight gain of rats fed MCT diet was 30% less than that of rats fed LF or LCT diets. Energy retention was less when the diet provided MCT than LCT or LF, and that resulted in a 60% decrease in the daily lipids deposition. Plasma glucose, free fatty acids, glycerol, and insulin/glucagon ratio were similar in the three groups. Blood ketone body (KB) concentrations in rats fed the high fat diets were extremely elevated, particularly in the MCT group, but declined throughout the experiment and by the 44th day hyperketonemia decreased by 50% but remained higher than in the LF diet. The blood beta-hydroxybutyrate/acetoacetate (B/A) ratio remained slightly elevated in rats fed the high fat diets. Similar changes were observed in liver KB concentration and in the B/A ratio. Liver lactate/pyruvate ratio elevated in the LCT and MCT groups at the initiation of the diets decreased by 50% at the end of the experiment. The consumption of high fat diets led to a 1.5-fold increase in liver PEPCK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Development of gluconeogenesis from various precursors in isolated rat hepatocytes during starvation or after feeding a high protein, carbohydrate-free diet.

Gluconeogenesis from dihydroxyacetone (DHA), glycerol, lactate, pyruvate or alanine was studied in the absence or in the presence of glucagon in hepatocytes isolated from starved rats or from rats fed a high protein diet for 2-48 h. In both groups, gluconeogenesis from DHA, glycerol, lactate and pyruvate exhibited similar changes over 48 h; the rates of glucose production increased progressively until 24 h and then plateaued. During the early phase (2-11 h), gluconeogenesis from DHA and glycerol were higher than gluconeogenesis from lactate and pyruvate. During the first 24 h of the experiment, gluconeogenesis from alanine displays a kinetic similar to that from lactate or pyruvate. After feeding a high protein diet for 24 to 48 h, gluconeogenesis from alanine was slightly higher than that in starved rats and paralleled the increase in alanine aminotransferase activity. Glucagon stimulated gluconeogenesis from DHA up to 48 h, but with glycerol this effect occurred only during the early phase (2-11 h). Glucagon stimulated gluconeogenesis from lactate, pyruvate or alanine by 1.35-fold throughout the experimental period. These findings suggest that the development of gluconeogenesis during starvation or after feeding a high protein diet displays different kinetics, depending on the substrate used and on the level of entry in the gluconeogenic pathway: triose phosphates or pyruvate.

Animals↗

PubMed1986

Studies on the early changes in rat hepatic fructose 2,6-bisphosphate and enzymes in response to a high protein diet.

Pertinent hepatic metabolites and enzymes were examined in rats fed a high carbohydrate (HC) diet and during the first 24 h of either starvation or feeding a high protein (HP) diet. Consumption of the HC diet induced slight but definite 24-h oscillations in hepatic concentrations of cyclic AMP, glycogen, glucose 6-phosphate, fructose 2,6-bisphosphate, fructose 1,6-bisphosphate and phosphoenolpyruvate, as well as the activities of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase and phosphoenolpyruvate carboxykinase. The transition to starvation or the HP diet induced, within 12 h, concurrent increases in cyclic AMP and phosphoenolpyruvate and decreases in glycogen, glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate and fructose 1,6-bisphosphate. These changes were associated with a decrease in the ratio of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and an increase in phosphoenolpyruvate carboxykinase. These results suggest that the activity of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle is similar during the first 24 h of starvation or HP consumption.

Analysis of Variance↗

PubMed1986

Development of gluconeogenesis from different substrates in newborn rabbit hepatocytes.

The rates of glucose production from various substrates entering gluconeogenesis at different steps were investigated in hepatocytes isolated from term-fetus and newborn rabbits fasted during the first 2 days of life. The data were compared to the rate of glucose production measured in hepatocytes from young rabbits (50-60 days) starved for 48 h. The net production of glucose from substrates (lactate, pyruvate, propionate, alanine) entering gluconeogenesis below phosphoenolpyruvate was very low at birth and increased during the first day of life, in relation with an increased cytosolic phosphoenolpyruvate carboxykinase activity. The net production of glucose from precursors entering gluconeogenesis at the level of triose phosphates (dihydroxyacetone, fructose) was low at birth but a maximal capacity for gluconeogenesis was reached within 6 h after birth. This enhanced gluconeogenic capacity was associated with a fall in hepatic fructose 2,6-bisphosphate concentration and a reduced glycolytic flux. In contrast, a high glucose production from galactose was already present at birth and did not rise at 24 or 48 h after delivery. These results suggest that the development of gluconeogenic capacity in hepatocytes isolated from newborn rabbit is dependent upon two factors, a decrease in the F2,6-P2 concentration which reduces the glycolytic flux and an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase.

Animals↗