PubMed Health⌕ Search

Biomedical subjects

C Demigne

Publications and source records attributed to C Demigne.

At least 19 recordsLinked to original sources
PubMed1994

Importance of the modulation of glycolysis in the control of lactate metabolism by fatty acids in isolated hepatocytes from fed rats.

In liver cells from fed rats, lactate utilization depends on its extracellular concentration and the threshold concentration at which lactate uptake equilibrates release is about 3 mM. Even-chain fatty acids (butyrate, octanoate, or oleate) played a crucial role (i) to depress the lactate release, from 40% (butyrate or oleate) to 72% (octanoate), and (ii) to lower the threshold concentration for lactate utilization (down to 1 mM with octanoate). The effects of fatty acids were connected to their inhibition of hepatic glycolysis, estimated by the detritiation of [6-3H]glucose (about -30% with butyrate or oleate and -45% with octanoate). Fatty acids depressed the cellular concentration of pyruvate which, at physiological concentration of lactate, favors its utilization. The rise in ketone bodies concentration in response to fatty acids reflected an enhanced acetyl CoA production, resulting in an accumulation of citrate. In parallel there was a drop of the cellular concentration of fructose 2,6-biphosphate. As a result, there was an inhibition of the flux through 6-phosphofructo-1 kinase (50, 75, or 40% inhibition with butyrate, octanoate, or oleate, respectively). The other regulatory glycolysis steps, catalyzed by glucokinase and pyruvate kinase, were not affected by fatty acids. Inhibition of hepatic glycolysis by fatty acids seems connected to acetyl-CoA generation since octanoate, readily metabolized to acetyl-CoA and ketone bodies by hepatocytes, had a more potent stimulatory effect on the hepatic uptake of lactate than butyrate or oleate. Propionate, which yields practically no acetyl CoA, slightly stimulated lactate release and elevated the threshold of lactate utilization. The present data suggest thus that, in hepatocytes from fed rats, fatty acids effectively inhibit glycolysis and switch liver cell metabolism toward gluconeogenic conditions, which promotes lactate utilization.

Acetyl Coenzyme A↗
PubMed1994

Control of lactate utilization by extracellular pH in isolated rat liver cells.

This study reports the influence of external pH on lactate balance in hepatocytes isolated from fed and 24-hour-starved rats. The effects of changes in extracellular pH on the utilization of lactate by liver cells has been studied in conditions simulating metabolic acidosis (pH 7.15, 10 mmol/L bicarbonate). The addition of lactate to a suspension of liver cells from fed rats shifted the lactate balance from net release to net utilization; the threshold of this shift was about 3 mmol/L in the presence of 10 mmol/L glucose. In these cells, acidic external pH (7.15) played a crucial role in stimulating the lactate utilization as shown by (1) a diminished release of lactate in the absence of lactate addition (-60%); (2) a marked decrease of the threshold of lactate utilization down to 1.2 mmol/L; and (3) a net stimulation of the lactate utilization for concentrations in the physiologic range (2 to 3 mmol/L). The effect of acidosis was mediated by an inhibition of glycolysis (-40%). Besides that, at pH 7.45, the addition of 100 mumol/L AICA-riboside 5-amino-4-imidazolecarboxamide riboside, (an inhibitor of hepatic glycolysis) mimicked the effect of acidosis. Moreover, differences in lactate fluxes between the two pH conditions were decreased in the absence of glucose. In liver cells from starved rats, regardless of the concentration of added lactate, the lactate balance was always directed toward net utilization. Accordingly, a change in external pH from 7.45 to 7.15 had a lesser effect on lactate metabolism than in liver cells from fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoimidazole Carboxamide↗
PubMed1993

Fatty acids are potent modulators of lactate utilization in isolated hepatocytes from fed rats.

This work reports the roles of the concentration of lactate and of fatty acids on lactate uptake by liver cells isolated from fed or 24-h starved rats. Hepatocytes isolated from fed rats released lactate and pyruvate. The addition of lactate shifted the lactate balance from net release to net utilization, with a threshold at approximately 2 mM. Lactate favored its own utilization by 1) increasing the lactate-to-pyruvate ratio (L/P) and 2) inhibiting hepatic glycolysis. The addition of oleate to the cells elicited 1) a net reduction of the release of lactate and pyruvate in basal conditions, 2) a marked decrease in the threshold of lactate utilization, down to values close to 0.5 mM, and 3) an important stimulation of the utilization of lactate, at physiological concentrations of 2-3 mM. These changes in lactate utilization induced by oleate were accompanied by a parallel increase of the L/P. Oleate acted by decreasing the cellular concentrations of pyruvate. Such an effect was mediated by 1) an inhibition of glycolysis and 2) a rise in pyruvate utilization toward glucose. Moreover, it seems that the capacity of various fatty acids to stimulate lactate utilization depends on their rate of oxidation by the liver. In liver cells isolated from 24-h starved rats, in keeping with the activation of gluconeogenesis, lactate was utilized by hepatocytes even at low concentrations. Because of the low glycolysis and of the high utilization of pyruvate in these cells, the presence of oleate only induced a moderate increase of lactate utilization (+32%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1993

Dietary protein paradox: decrease of amino acid availability induced by high-protein diets.

The aim of the present study was to evaluate the effect of changes in dietary protein level on overall availability of amino acids for tissues. For this purpose, rats were adapted to diets containing various concentrations of casein (7.5, 15, 30, and 60%) and were sampled either during the postprandial or postabsorptive period. In rats fed the protein-deficient diet, glucogenic amino acids (except threonine) tended to accumulate in plasma, liver, and muscles. In rats fed high-protein diets, the hepatic balance of glucogenic amino acids was markedly enhanced and their liver concentrations were consistently depressed. This response was the result of a marked induction of amino acid catabolism (a 45-fold increase of liver threonine-serine dehydratase activity was observed with the 60% casein diet). The muscle concentrations of threonine, serine, and glycine underwent changes parallel to plasma and liver concentrations, and a significant reduction of glutamine was observed. During the postabsorptive period, adaptation to high-protein diets resulted in a sustained catabolism of most glucogenic amino acids, which accentuated the drop in their concentrations (especially threonine) in all the compartments studied. The time course of metabolic adaptation from a 60 to a 15% casein diet has also been investigated. Adaptation of alanine and glutamine metabolism was rapid, whereas that of threonine, serine, and glycine was delayed and required 7-11 days. This was paralleled by a relatively slow decay of liver threonine-serine dehydratase (T-SDH) activity in contrast to the rapid adaptation of pyruvate kinase activity after refeeding a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Control of glycogen metabolism by gluconeogenic and ketogenic substrates in isolated hepatocytes from fed rats.

1. This study was conducted to examine the effects of gluconeogenic and ketogenic substrates on the activities of the glycogen-metabolizing enzymes and on glycogenolysis in isolated hepatocytes from fed rats. 2. Gluconeogenic substrates like fructose, dihydroxyacetone or lactate turned out to stimulate the glucose-induced activation of glycogen synthase and this effect may be linked, to some extent, to the increase of the cellular glucose 6-phosphate concentration. 3. The effect of fructose was accompanied by the onset of glycogen synthesis. 4. Energetic substrates like fatty acids were also potent activators of glycogen synthase, especially in the presence of glucose. 5. When fatty acids were added alone or together with a physiological concentration of glucose, they induced or potentiated the inhibition of glycogen phosphorylase-a. 6. This inhibitory effect was mediated by a decrease of lactate release. 7. The stimulatory effect of amino acids on glycogen synthase seemed to be direct, non mediated by an inhibition of the phosphorylase-a activity although hepatic glycogenolysis markedly decreased. 8. Moreover, the amino acid action could be linked to their capacities to induce cell swelling and/or to limit proteolysis.

Amino Acids↗
PubMed1992

Expression of R-3-hydroxybutyrate dehydrogenase, a ketone body converting enzyme in heart and liver mitochondria of ruminant and non-ruminant mammals.

1. The properties of rat liver and bovine heart R-3-hydroxybutyrate dehydrogenase (BDH) have been extensively studied in the past 20 years, but little is known concerning the biogenesis and the regulation of this dehydrogenase over different species. 2. In addition, controversial results were often reported concerning the activity, the level and the subcellular location of this enzyme in ruminants. 3. BDH activity found in liver and kidney mitochondria from ruminants (cow and sheep) is low, while it is much higher in rat. 4. However, the enzyme activity is detected in microsomes and in cytosol of liver and of kidney cells from ruminants. These activities are not correlated to ketonaemia level. 5. Although low BDH activity is detected in liver mitochondria from ruminants; the bovine liver BDH gene seems to be translated since BDH can be immunodetected by using an antiserum raised against bovine heart BDH. 6. Beside this, the good cross-reactivity between heart BDH and liver BDH suggests their high level of homology in ruminants.

Animals↗
PubMed1990

Non-hormonal and hormonal control of glycogen metabolism in isolated sheep liver cells.

1. Control of glycogen metabolism by various substrates and hormones was studied in ruminant liver using isolated hepatocytes from fed sheep. 2. In these cells glucose appeared uneffective to stimulate glycogen synthesis whereas fructose and propionate activated glycogen synthase owing to (i) a decrease in phosphorylase a activity and (ii) changes in the intracellular concentrations of glucose 6-phosphate and adenine nucleotides. 3. The activation of hepatic glycogenolysis by glucagon and alpha 1-adrenergic agents was associated with increased phosphorylase a and decreased glycogen synthase activities. 4. The simultaneous changes in these two enzyme activities suggest that in sheep liver, activation of phosphorylase a is not a prerequisite step for synthase inactivation. 5. In sheep hepatocytes, in the presence of propionate and after a lag period, insulin activated glycogen synthase without affecting phosphorylase a. 6. This latter result suggests that the direct activation of glycogen synthase by insulin is mediated by a glycogen synthase-specific kinase or phosphatase. Insulin also antagonized glucagon effect on glycogen synthesis by counteracting the rise of cAMP.

Animals↗
PubMed1990

The effect of high-fibre diet on plasma lipoproteins and hormones in genetically obese Zucker rats.

The effects of prolonged substitution of readily digested carbohydrates (wheat starch) for poorly digested carbohydrates (mixture of various fibres and crude potato starch) on plasma lipids, lipoproteins and hormones were investigated in Zucker, genetically obese rats. Lean rats were also studied in parallel. Usually, plasma lipid and insulin levels and insulin/glucose ratio were higher in obese rats vs. their lean littermates. High-fibre diet intake led to weight loss in both obese and lean rats. With a high-fibre diet, plasma lipid, insulin and glucose postprandial levels in both groups were reduced when compared with their respective control animals. Dietary fibre modified the lipoprotein profile. Triglycerides and cholesterol were reduced in all studied lipoprotein fractions. The study of high density lipoprotein (HDL) fraction in rats fed a high-fibre diet demonstrated a decrease in the HDL1 subpopulation and in the apolipoprotein (apo)E proportion. The findings show that a high-fibre diet modulates plasma lipid, insulin and glucose levels and modifies the plasma lipoprotein distribution and composition in normolipaemic, lean rats as well as in hyperlipaemic, genetically obese rats.

Animals↗
PubMed1990

Fluxes and membrane transport of amino acids in rat liver under different protein diets.

The aim of the present work was to evaluate in vivo the role of the transport step in hepatic amino acid metabolism. To vary hepatic utilization of amino acids, rats were adapted to diets containing various concentrations of casein (5, 15, and 60%). In rats fed 5 or 15% casein diets, Gln and Glu were released by the liver, and there was a significant uptake of Ala. Hepatic fluxes of amino acids increased considerably after adaptation to high-casein diet (up to 1.55 mumol.min-1.g liver-1 for Ala), because of the rise in afferent concentrations as well as enhanced uptake percentage (peaking at 60-75% for most glucogenic amino acids). Adaptation to a high-protein diet led to induction of not only system A but also of most of the other transport systems (Gly, anionic, T, y+, and to a lesser extent system N); only systems ASC and L were unchanged. The study of amino acid repartition between liver and plasma with different diets indicates that transport could modulate utilization of Ala, Ser, Thr, Gly, Gln, and Asp. For Arg and Asn, present in very low concentrations in liver under any condition, the transport step should be the major locus of control of their metabolism. For amino acids chiefly transported by nonconcentrative systems, such as aromatic amino acids, cellular metabolism could also be limited by the transport process. In conclusion, during adaptation to a high-protein diet, there is apparently a coordinated adaptation of amino acid transport and of their intracellular metabolism. For some amino acids, induction of catabolic enzymes seems greater than that of transport, so that the transport step may play an important role in control of metabolic fluxes. For example, concentration of amino acids such as Thr may be markedly depressed in rats adapted to a high-protein diet.

Amino Acids↗
PubMed1988

Modulation of glucagon effects by changes in extracellular pH and calcium.

We have examined the influence of extracellular pH and calcium concentration on the action of glucagon on isolated rat hepatocytes, perfused liver or plasma membrane preparations. Incubation of rat hepatocytes with 10 nM glucagon at pH 7.4 caused an immediate increase in cAMP concentrations (8-fold), and this rise was almost 50% lower at acidic extracellular pH (6.9). This effect of pH could not be explained by an alteration of the hormone binding to its receptor for glucagon concentrations higher than 1 nM. The effect of acidosis on cAMP production was still present with non-hormonal effectors, such as 10 microM Gpp[NH]p, 30 microM forskolin or 10 mM NaF. This suggests a direct action of acidosis on the regulatory component Ns and/or on the catalytic subunit of adenylate cyclase. Acidic pH also depressed mitochondrial processes responsive to glucagon (NAD(P)H fluorescence, glutamine breakdown). Whatever the experimental model, calcium appeared to be required for maximal stimulation of cAMP production by glucagon. On perfused rat liver, glycogenolysis was depressed in the absence of extracellular calcium in the perfusate. In isolated hepatocytes, the stimulation of phosphorylase alpha activity by glucagon was modulated by extracellular calcium concentrations lower than 0.2 mM. This suggests that, although glucagon action is chiefly cAMP-mediated, its effect on calcium mobilization (affecting various cellular process, including cAMP production itself) should also be taken into account. This work also confirmed the importance of calcium in the stimulation of mitochondrial metabolism of glutamine by glucagon.

Adenylyl Cyclases↗
PubMed1988

Characterization of glucagon and catecholamine effects on isolated sheep hepatocytes.

The purpose of this study was to characterize the glycogenolytic response to catecholamines and glucagon in isolated sheep hepatocytes. In this species, epinephrine appeared to exert its action on hepatic glycogenolysis by altering the cytosolic concentrations of both adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+. In contrast to results obtained in rat hepatocytes, glucagon failed to induce a rise in free cytosolic Ca2+ in sheep liver. Experiments on isolated hepatocytes or on liver plasma membranes showed that in sheep, glucagon was more efficient than epinephrine in promoting the production of cAMP. In the presence of glucagon or epinephrine, the activation of the glycogen phosphorylase a always appeared greater in sheep than in rat liver cells, whereas the variations in cellular cAMP were quite limited in sheep. The alpha 1- and beta-agonists (phenylephrine and isoproterenol) were alone as efficient as epinephrine in promoting phosphorylase a activation in sheep hepatocytes. All these results indicate the existence in sheep liver of a glycogen phosphorylase highly responsive to hormones.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Changes in glucose and lipid metabolism in starved or starved-refed Japanese quail (coturnix coturnix japonica) in relation to fine structure of liver cells.

1. Metabolic response of adult quail to fasting or refeeding was studied by measuring the main blood and hepatic metabolites. Moreover, the fine structure of hepatocytes in these physiological conditions was described. 2. Starvation or refeeding did not affect glycemia in male as in female quails. 3. Fasting had no effect on plasma free fatty acids in female quails, whereas plasma triglycerides were markedly decreased. 4. In fasted quails, there was an active ketogenesis with a high 3-hydroxybutyrate/acetoacetate ratio. 5. Ultrastructural aspect of liver parenchymal cells from fasted quails revealed alterations in the quantity of glycogen, smooth endoplasmic reticulum, lysosomes and in the form of the rough endoplasmic reticulum. 6. The significance of these morphological changes was discussed in relation to an hormonal stimulation.

Animals↗
PubMed1983

Control of hepatic utilization of serine, glycine and threonine in fed and starved rats.

Effects of varying protein level on hepatic utilization of serine, threonine and glycine were examined by measurements of metabolic fluxes across the liver. Feeding a high protein (HP) diet markedly enhanced hepatic extraction of serine, threonine and glycine, in parallel to alanine. After 20 hours starvation, activity of alanine aminotransferase and serine dehydratase still reflected the induction of these enzymes in fed rats. Thus, in starved rats previously adapted to HP diets, hepatic uptake of serine, threonine and glycine remained very efficient. With a normal diet, gluconeogenesis from alanine may be very active during starvation, in contrast to serine. The present results suggest that serine, and, to a lesser extent glycine, are very efficient glucogenic substrates with HP diets. The serine aminotransferase pathway might be important in rats fed HP diets, particularly for utilization of serine synthesized from glycine in mitochondria. With HP diets, the drop in hepatic alanine, serine and threonine suggest that transport across the plasma membrane might limit their utilization.

Alanine↗
PubMed1983

Energy metabolism and thermoregulation in the newborn calf.

About half of calf losses occur during the first two days of life. Mortality rate is increased by difficult parturition and adverse climatic conditions. However, thermoregulatory mechanisms are operative at birth, these including the metabolism of brown adipose tissue, shivering and physical activity. Thermoregulation is just as effective in twin as in single calves provided that calving conditions are good. Heat production of Charolais and Salers calves was lower than that of Friesian; the difference came from a lower basal metabolic rate rather from a better thermic insulation. In dystocial calves, blood pH at birth was very low, lactataemia was two or three times higher than in eutocial calves, mobilization of body lipids was reduced and plasma thyroïd hormone level were low, which can explain the lower heat production and the drop in rectal temperature. The physiological responses of calves born by caesarean parturition depend on the delay incurred during surgical removal.

Animals↗
PubMed1982

Influence of unrefined potato starch on cecal fermentations and volatile fatty acid absorption in rats.

The effect of uncooked potato starch in the diet on cecal fermentation and absorption of volatile fatty acids and on changes in the digestive supply of nutrients were investigated. Dietary potato starch (25%) markedly increased cecal size and the cecal pool of volatile fatty acids. These were maximal in the postabsorptive state, whereas the most acidic cecal pH readings were observed during the late absorptive period. Compared to the basal diet, feeding potato starch did not change arterial concentrations of glucose, lactate or alanine. Nevertheless, blood acetate was increased, whereas plasma triglycerides and cholesterol were reduced. The digestive balance of nutrients was determined by measurements of portal blood flow and arteriovenous differences across the digestive tract: the digestive supply of glucose was maximal during the absorptive period, but was lower in rats fed the potato starch diet. The absorption of volatile fatty acids was strongly increased by feeding potato starch and was maximal in the postabsorptive state, whereas glucose absorption was finished. The volatile fatty acids the constituted the main source of energetic fuels coming from the digestive tract. These results indicate that the effect of potato starch on digestion and metabolism is similar to that of dietary fibers, and that the regular supply of large amounts of volatile fatty acids, particularly during the postabsorptive period, could bring about substantial changes in liver metabolism.

Alanine↗
PubMed1982

Glucose-stimulated insulin secretion in rats with normal plasma calcium levels: effects of calcium deficiency.

Weanling Wistar rats were pair-fed for 9 days a control or a calcium-deficient diet. After a 12-hour fast the rats were injected intraperitoneally with glucose (250 mg/100 g body weight), and blood was collected 15, 30 and 60 minutes after the injection. Before injection, calcium (9.7 +/- 0.2 mg/100 ml), glucose and insulin plasma levels were identical in the control and deficient animals, although calcium-deficient animals showed a small but significant increase in blood plasma magnesium levels. Blood glucose levels were higher in the calcium-deficient rats than in control rats 15 to 30 minutes after the glucose injection (15.4 +/- 1.4 vs. 9.7 +/- 0.4 mM, P less than 0.01, 30 minutes after). Plasma insulin levels were significantly lower 15 minutes after the glucose injection (24 +/- 4 vs. 73 +/- 8 microU/ml; P less than 0.01). Calcium deficiency is therefore associated with a decreased response to the glucose tolerance test in the absence of any change in the blood plasma calcium levels.

Animals↗
PubMed1976

Partition and absorption of valatile fatty acids in the alimentary canal of the rat.

The partition and absorption of volatile fatty acids (VFA) have been studied in the rat using a non purified diet comprising mainly a mixture of cereals and soya-bean meal. 2. The concentration of acetic and lactic acid was compared in non secretory (cul-de-sac) and secretory regions of the stomach. The greatest concentrations of both acids were found in the cul-de-sac region where the pH was highest (pH 5.0). 3. Concentration and absorption of VFA were negligible in the small intestine. 4. High VFA concentrations were found in the caecal contents, while lactic acid concentrations were lower. The volume and concentrations of the caecum contents varied little during the day and decreased rapidly during the first 24 h of fasting. 5. The concentrations of VFA, particularly that of butyric acid, were lower in the proximal colon than in the caecum. Caecumectomy caused a considerable decrease in VFA concentrations in the colon. 6. Arteriovenous differences in VFA and detone bodies were studied for the caecal and colon veins in rats. A close parallel between VFA concentration in the caecal contents and the arteriovenous differences was observed. In rat, ketogenesis was weak in the caecal wall (12 p. 100 of butyric acid absorption) and negligible in the colon wall. VFA are absorbed entirely in ionized form when caecal PH attains 7.5 in fasted rats. Special mechanism for caecal absorption should therefore be considered, perhaps linked with the large sodium transport in the caecum. 7. The relatively high VFA concentrations measured in the portal vein suggested that they are important in the digestive processes.

Animals↗