Luminal dietary protein, not amino acids, induces pancreatic protease via CCK in pancreaticobiliary-diverted rats

2000 ◽  
Vol 278 (6) ◽  
pp. G937-G945 ◽  
Author(s):  
Hiroshi Hara ◽  
Sumika Ohyama ◽  
Tohru Hira
Keyword(s):  
Amino Acids ◽  
Direct Action ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Intestinal Lumen ◽  
Casein Diet ◽  
Acid Diet ◽  
High Amino Acid ◽  
Pancreatic Proteases

We determined whether pancreatic adaptation to a high-protein diet depends on ingested protein in the intestinal lumen and whether such adaptation depends on a CCK or capsaicin-sensitive vagal afferent pathway in pancreaticobiliary-diverted (PBD) rats. Feeding a high-casein (60%) diet but not a high-amino acid diet to PBD rats increased pancreatic trypsin and chymotrypsin activities compared with those after feeding a 25% casein diet. In contrast, feeding both the high-nitrogen diets induced pancreatic hypertrophy in PBD rats. These pancreatic changes by the diets were abolished by treatment with devazepide, a CCK-A receptor antagonist. Protease zymogen mRNA abundance in the PBD rat was not increased by feeding the high-casein diet and was decreased by devazepide. Perivagal capsaicin treatment did not influence the values of any pancreatic variables in PBD rats fed the normal or high-casein diet. We concluded that luminal protein or peptides were responsible for the bile pancreatic juice-independent induction of pancreatic proteases on feeding a high-protein diet. The induction was found to be dependent on the direct action of CCK on the pancreas. Pancreatic growth induced by high-protein feeding in PBD rats may depend at least partly on absorbed amino acids.

Time Course of Enzyme Adaptation. III. Periodic and Nonperiodic Responses of Rat Liver Enzyme Activities to Diets in Meal-Fed Rats

1971 ◽  
Vol 49 (1) ◽  
pp. 108-118 ◽  
Author(s):  
B. Szepesi ◽  
R. A. Freedland
Keyword(s):  
Pyruvate Kinase ◽  
High Protein Diet ◽  
Periodic Variation ◽  
Maximum Activity ◽  
High Protein ◽  
Protein Diet ◽  
Liver Protein ◽  
Casein Diet ◽  
Phosphohexose Isomerase ◽  
Glucose 6 Phosphate Dehydrogenase

Enzymes associated with carbohydrate and amino acid metabolism as well as other liver constituents were studied in rats meal-fed, daily for 60 min, diets consisting of corn oil, salt, and vitamins plus 75% carbohydrate and 15% casein or a 90% casein diet. Relative liver size and the levels of liver glycogen and total and soluble liver protein were subject to periodic variation after the ingestion of a meal. They reached maximums about 6–12 h after the meal and then declined. In the rats fed the 90% casein diet the onset of increases was delayed after the first meal.The activity of glucose-6-phosphatase was increased by a fructose diet and the high-protein diet, but no periodicity was observed. The activities of fructose-1, 6-diphosphatase, dihydroxyacetone kinase, and malic enzyme were not subject to periodic variation, and these enzymes were not increased by the fructose or high-protein diets. Serine dehydrase activity was increased by the high-protein diet, but the question of periodicity cannot be resolved with the available data.The tyrosine–α-ketoglutarate transaminase activity in rats fed a 75% glucose – 15% casein diet was subject to periodic variation. Maximum activity occurred just before feeding, and minimum activity 12 h after feeding. In the rats fed the 90% casein diet the activity of the enzyme was considerably increased, and was already maximum 3 h after the meal. The activity then decreased to a relatively high minimum 12 h after the meal, at which time it began to increase again.The activities of pyruvate kinase, glucose-6-phosphate dehydrogenase, and phosphohexose isomerase were all subject to periodicity in the glucose-fed rats. In the rats fed the high-protein diet, there was a periodic response in activity of both pyruvate kinase and glucose-6-phosphate dehydrogenase after the first meal; but enzyme activity remained minimum after the second meal. Glucose-6-phosphate dehydrogenase and phosphohexose isomerase activities were increased after three meals of the fructose diet, and were higher than in glucose-fed rats even 24 h after a meal. Maximum activity of these three enzymes occurred 12 h after the meal. There was only small periodicity in the activity of glutamic–pyruvic transaminase. The activity of this enzyme was increased by the high-protein diet and also by the high-fructose diet, although the latter effect was only temporary. The possible importance of certain types of adaptations in meal-fed rats was discussed in connection with physiological requirements.

scholarly journals Colorectal cancer progression is potently reduced by a glucose-free, high-protein diet: comparison to anti-EGFR therapy

2021 ◽  
Author(s):  
Kerstin Skibbe ◽  
Ann-Kathrin Brethack ◽  
Annika Suenderhauf ◽  
Mohab Ragab ◽  
Annika Raschdorf ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cell ◽  
Aerobic Glycolysis ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Intestinal Barrier Function ◽  
High Amino Acid ◽  
Tumor Load

Background & Aims: To enable rapid proliferation, colorectal tumor cells up-regulate epidermal growth factor receptor (EGFR) signaling and perform high level of aerobic glycolysis, resulting in substantial lactate release into the tumor microenvironment and impaired anti-tumor immune responses. We hypothesized that an optimized nutritional intervention designed to reduce aerobic glycolysis of tumor cells may boost EGFR-directed antibody (Ab)-based therapy of pre-existing colitis-driven colorectal carcinoma (CRC). Methods: CRC development was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) administration to C57BL/6 mice. AOM/DSS treated mice were fed a glucose-free, high-protein diet (GFHPD) or an isoenergetic control diet (CD) in the presence or absence of i.p. injection of PBS, an irrelevant control mIgG2a or an anti-EGFR mIgG2a. Ex vivo, health status, tumor load, metabolism, colonic epithelial cell differentiation and immune cell infiltration were studied. Functional validation was performed in murine and human CRC cell lines MC-38 or HT29-MTX. Results: AOM/DSS treated mice on GFHPD displayed reduced systemic glycolysis, resulting in improved tumoral energy homeostasis and diminished tumor load. Comparable but not additive to an anti-EGFR-Ab therapy, GFHPD was accompanied by enhanced tumoral differentiation and decreased colonic PD-L1 and splenic PD-1 immune checkpoint expression, presumably promoting intestinal barrier function and improved anti-tumor immune responses. In vitro, glucose-free, high-amino acid culture conditions reduced proliferation but improved differentiation of CRC cells in combination with down-regulation of PD-L1 expression. Conclusion: We here found GFHPD to metabolically reprogram colorectal tumors towards balanced OXPHOS, thereby improving anti-tumor T-cell responses and reducing CRC progression with a similar efficacy as EGFR-directed antibody therapy.

Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo experiments using a model of isolated perfused liver

2008 ◽  
Vol 294 (3) ◽  
pp. R748-R755 ◽  
Author(s):  
M. Jourdan ◽  
L. Cynober ◽  
C. Moinard ◽  
M. C. Blanc ◽  
N. Neveux ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ex Vivo ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Urea Production

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.

Liver ornithine decarboxylase in pregnant rats fed two levels of casein

1983 ◽  
Vol 244 (6) ◽  
pp. E548-E554
Author(s):  
Y. Hitier ◽  
O. Champigny ◽  
G. Bourdel
Keyword(s):  
Ornithine Decarboxylase ◽  
High Protein Diet ◽  
Tyrosine Aminotransferase ◽  
High Protein ◽  
Protein Diet ◽  
Casein Diet ◽  
Pregnant Rats ◽  
Pregnant Females ◽  
Postprandial Phase ◽  
Different Levels

Liver ornithine decarboxylase (ODC) and tyrosine aminotransferase (TAT) activities were assessed at 2200 h (prandial phase) and at 1000 h (postprandial phase) in virgin and in pregnant (day 13-20) rats fed on different levels of casein and carbohydrate. In virgin rats, ODC levels were higher at 2200 h after resumption of eating than at 1000 hours, the inductive effect being greater with the high-casein than with the low-casein diet. Rapid deinduction followed termination of eating, resulting in equally low enzyme levels at 1000 h with both diets. On the contrary, prandial and postprandial levels of TAT were always greater with the high-protein diet. In pregnant rats, there was a progressive stimulation of ODC that reached a maximum on day 19. However, the inductive capacity of the high-protein diet was lower than that of the low-casein diet. Prandial rest was not followed by enzyme deinduction at 1000 h. In contrast, TAT stimulation remained dependent on overall casein ingestion. At constant casein but restricted carbohydrate intake, pregnant females exhibited a reduction in ODC stimulation. Thus, whereas in virgin females proteins are determinant in the regulation of ODC, during pregnancy there determinant in the regulation of ODC, during pregnancy there is a shift toward modulation by carbohydrates. Levels of liver urea and ornithine were found to vary in inverse proportion with the magnitude of ODC stimulation.

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

1990 ◽  
Vol 259 (5) ◽  
pp. E614-E625 ◽  
Author(s):  
P. Fafournoux ◽  
C. Remesy ◽  
C. Demigne
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Aromatic Amino Acids ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Transport Systems ◽  
Low Concentrations ◽  
Significant Uptake

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.

High Protein Diet and Phenylalanine Hydroxylase Activities in Rats

Pteridines ◽  
1989 ◽  
Vol 1 (4) ◽  
pp. 235-238 ◽  
Author(s):  
Michael P. Carty ◽  
Edel Beirne ◽  
John Donlon
Keyword(s):  
Rat Liver ◽  
Phenylalanine Hydroxylase ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Casein Diet ◽  
Dependent Activity ◽  
Liver And Kidney ◽  
Phenylalanine Metabolism

SummaryThe effects of a diet of 85% casein on the activities of the phenylalanine hydroxylases of rat liver and kidney have been compared. Whereas only the tetrahydrobiopterin-dependent activity of rat hepatic phenylalanine hydroxylase is significantly stimulated, both the tetrahydrobiopterin-dependent and the dimethyltetrahydropterin- dependent activities of the renal enzyme are significantly decreased, after five days of feeding a casein diet. The animals fed a high protein diet for seven days have an increased rate of phenylalanine catabolism in vivo, which is also reflected in increased flux of label from phenylalanine into glucose. The regulation of phenylalanine metabolism, under these conditions, is discussed.

scholarly journals Stimulation of amino acid transport into liver cells from rats adapted to a high-protein diet

1982 ◽  
Vol 206 (1) ◽  
pp. 13-18 ◽  
Author(s):  
P Fafournoux ◽  
C Rémésy ◽  
C Demigné
Keyword(s):  
Amino Acids ◽  
Decisive Role ◽  
High Protein Diet ◽  
Isolated Hepatocytes ◽  
Hepatic Uptake ◽  
High Protein ◽  
Protein Diet ◽  
High Protein Diets ◽  
Protein Diets

After adaptation of rats to a 90%-casein diet, hepatic uptake of alanine is strikingly increased in vivo, with concomitant appearance of a concentration of favourable for uptake. With a high-protein diet, uptake of 2-aminoisobutyrate by isolated hepatocytes in the presence of various concentrations of substrates suggested induction of the A system (high-affinity system), whose emergence has been reported during starvation or after glucagon treatment. The other system (ASC, L) were characterized: induction processes only affected the A system. Dibutyryl cyclic AMP addition resulted in an increase in 2-aminoisobutyrate transport at low substrate concentration, the response being greater after adaptation to a high-protein diet. Evidence is presented suggesting that the increased uptake of amino acids by the liver of rats fed on high-protein diets is obtained by developing favourable gradients and enhancing transport capacities. These adaptations allow sufficient amounts of amino acids to enter the liver, where accelerated metabolism plays a decisive role.

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