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C Remesy

Publications and source records attributed to C Remesy.

33 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Magnesium absorption in the caecum of rats related to volatile fatty acids production.

Rats were fed with a semi-synthetic diet with or without raw potato starch. (The level of minerals was the same in the two diets.) Because of its special structure raw potato starch was not attacked by rat enzymes. The rats fed on the raw potato starch diet showed increase in caecal weight. The increase in caecal volatile fatty acids (VFA) and decrease in pH were evidence of increased microbial fermentation from the presence of substrate in the caecum. There was also an increase in the arteriovenous difference in VFA and Mg in the caecum. Nutritional balance study was performed and confirmed the better Mg absorption in rats fed on the raw potato starch diet. The lower parts of the digestive tract seem to play an important role in Mg absorption and further studies on the relations between caecal volume, pH, VFA, microbial activity and Mg absorption are necessary.

Animals↗

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↗

Determination of volatile fatty acids in plasma after ethanolic extraction.

1. A new rapid micro-method for measuring plasma volatile fatty acids is described. The volatile fatty acids are extracted from plasma with ethanol in the presence of a known quantity of internal standard (sodium isobutyrate). After evaporation of the ethanolic solution of the sodium salts, the residue is dissolved in a dilute solution of orthophosphoric acid to permit analysis by g.l.c. 2. A technique of g.l.c. analysis is described which permits the separation of all the volatile fatty acids from the other plasma constituents at temperatures below 100 degrees C in 5 min. 3. Steam-distillation techniques are unsatisfactory when the acetic acid concentrations in the plasma are below 0.2mm. Heating of a number of plasma constituents in acid conditions gives rise to acetic acid. 4. The binding of volatile fatty acids to plasma proteins was studied; this binding is negligible for acetic acid, but increases with the length of the fatty acid carbon chain. 5. The limits of use of the method and the physiological implications are discussed.

Animals↗