scholarly journals The effect of fasting on enzyme levels in the enlarged and involuting rat pancreas

1987 ◽  
Vol 58 (3) ◽  
pp. 427-436 ◽  
Author(s):  
R. A. Crass ◽  
P. S. Oatesa ◽  
R. G. H. Morgan

1. The effect on pancreatic digestive enzyme levels of fasting and changes from a diet containing trypsin inhibitor (raw soya-bean flour, RSF) to diets free of trypsin inhibitor (heated soya-bean flour, HSF, or commercial rat chow) was studied in rats for up to 7 d.2. In RSF-fed rats killed without fasting, enzyme levels were low, but after fasting for 24 h before killing there was a marked increase in all enzyme levels. Histological studies showed that pancreatic acinar cells from RSF-fed rats killed without fasting were devoid of zymogen granules, but following a 24 h fast there was a marked accumulation of zymogen granules which extend into the basal cytoplasm. Fasting either produced no change or a fall in enzyme levels in rats fasted after feeding HSF or chow continuously.3. If animals fed on RSF were changed to HSF and either fed or fasted for 24 h up to the time of killing there was an increase in amylase (EC3. 2. 1. 1), trypsin (EC3. 4. 21. 4), lipase (triacylglycerol lipase;EC3. 1. 1. 3) and protein 1 d after the change, followed by a fall over the next 6 d to levels similar to those seen in rats fed on HSF continuously.4. Animals changed from RSF to chow showed similar effects as far as trypsin, lipase and protein were concerned, but amylase rose, to reach the level seen in rats fed on chow continuously (about ten times that seen in soya-bean-fed rats), after 2 d.5. These results suggest that in the rats fed on RSF, pancreatic enzyme synthesis is rapid but secretion is equally rapid and intracellular enzyme levels are low. When these animals are fasted or changed to a diet free of trypsin inhibitor the rate of secretion falls but the high rate of synthesis continues for at least 24 h and enzymes accumulate in the pancreas. In studies of pancreatic enzyme levels in rats fed on trypsin inhibitor the extent of fasting before killing the animal is therefore an important variable. Such animals should probably not be fasted before study.

1987 ◽  
Vol 58 (2) ◽  
pp. 175-179 ◽  
Author(s):  
John Calam ◽  
Joanna C. Bojarski ◽  
Caroline J. Springer

1. The aim of the present study was to determine whether oral ingestion of raw soya-bean flour, which contains trypsin inhibitors, alters the release of cholecystokinin (CCK) in man.2. Eleven healthy volunteers ate two mixed meals: one with raw soya-bean flour and the other with soya-bean flour that had been heat-treated. The two flours inhibited 34 and 3 mg trypsin/g flour respectively.3. CCK was measured in plasma using a bioassay based on the release of amylase (EC 3.2.1.1) from dispersed rat pancreatic acini.4. The peak CCK response was 168 (SE 8.1) pmol/l with raw soya-bean flour but 4.9 (SE 2.8) pmol/l with heat-treated flour (P < 0.05).5. We conclude that ingestion of raw soya-bean flour increases CCK release in man and that heat treatment which reduces the trypsin inhibitor content of the flour also diminishes its CCK-releasing effect.


2006 ◽  
Vol 82 (5) ◽  
pp. 645-651 ◽  
Author(s):  
J. J. Zang ◽  
D. F. Li ◽  
J. R. Wang ◽  
S. S. Tang ◽  
X. L. Li ◽  
...  

AbstractThis study was conducted to examine the relationship between soya-bean agglutinin and cholecystokinin in stimulating pancreatic enzyme synthesis in rats. In experiment 1, 30 rats were given daily gastric infusions of 0, 3·5, 7·0, 10·5, or 14·0 mg of soya-bean agglutinin (no.=6) for 14 days. Compared with the control group, soya-bean agglutinin reduced weight gains, enhanced absolute and relative dry pancreatic weights, elevated serum cholecystokinin levels, and stimulated cholecystokinin mRNA expression in the intestine (P<0·001). Pancreatic nucleic acid composition and the pancreatic activities of the enzymes amylase, trypsin and chymotrypsin all increased in response to increasing levels of soya-bean agglutinin (P<0·001). In experiment 2, duodenal cells obtained from two rats were incubated at 37°C with either saline, 100 μg/ml soya-bean agglutinin, or a mixture of 100 μg/ml soya-bean agglutinin and 10 mmol/m of the L-type, calcium channel antagonist verapamil. Soya-bean agglutinin stimulated cholecystokinin mRNA expression and cholecystokinin release from small intestinal mucosal cells, and the effect was attenuated by verapamil. In experiment 3, pancreatic acinar cells, obtained from three rats, were incubated at 37 °C with either saline, or cholecystokinin (100 fmol/ml) and soya-bean agglutinin (1000 fmol/ml), either alone or in combination. Amylase, trypsin, and chymotrypsin activities from both culture media and acini cells were stimulated by both the soya-bean agglutinin and the cholecystokinin treatments. Enzyme activities, when the two factors were incubated in combination, were intermediate to those obtained when the factors were incubated alone. This suggesting that soya-bean agglutinin may depress the action of cholecystokinin on pancreatic enzymatic activities. In summary, soya-bean agglutinin appears to stimulate pancreatic enzyme synthesis both directly and also through a cholecystokinin-mediated pathway.


1962 ◽  
Vol 12 (2) ◽  
pp. 313-327 ◽  
Author(s):  
Bernard Weisblum ◽  
Lawrence Herman ◽  
Patrick J. Fitzgerald

After 10 days of a protein-free diet the acinar cells of the rat pancreas showed a coarsening of nuclear matrix, depletion of zymogen granules, some loss of ribosomes, and a widening of the spaces between ergastoplasmic membranes. In addition, there could be found, but rarely, a lesion of the ergastoplasm consisting of vacuoles of agranular, disoriented membranes, which was similar to a lesion produced by ethionine. Thereafter, a return toward normal structure occurred which was characterized by beginning increase in the size of the Golgi apparatus at 12 days, appearance of zymogen granules at 18 days, and a relatively normal appearing but smaller cell at 28 days. After 10 to 12 days of protein deprivation a reversal of many of the morphologic effects of protein deprivation was accompanied by a return toward normal of some pancreatic enzyme activities. Possibly this spontaneous return toward normal levels represented a raiding of protein stores, or it may have been an adaptive phenomenon.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 236-236
Author(s):  
Tatsuo Ito ◽  
Ryuichiro Doi ◽  
Shinji Uemoto

236 Background: Sorafenib is an oral multi-kinase inhibitor which is regarded as a key drug for HCC and RCC. It has been unexpectedly found that the compound causes an increase of serum pancreatic enzyme levels without clinically recognized pancreatitis. The reason for this event is not well understood yet. The aim of this study was to clarify the mechanisms involved in this phenomenon. Methods: Eight-week old BALB/cA male mice were used in in vivo studies. Sorafenib tosylate was administered per os once daily at a dose of 150 mg/kg body weight. Control mice were given vehicle alone. Mice were sacrificed 24 hr after 1-, 2-, 3- and 7-day administration of the compound, and blood samples and pancreatic tissue samples were obtained (n=5 for each group). The tissue samples were used for hematoxylin and eosin (HE) staining, immunohistochemistry, electron microscopy (EM), western blot and RT-quantitative PCR studies. Results: Serum amylase levels were elevated after sorafenib administration. The amylase level hit the peak after 2-day administration, and then gradually decreased. By HE staining, the control group without sorafenib showed a basophilic stained area in the baso-lateral site of the acinar cells. In contrast, the acinar cytoplasm after 2-day administration of sorafenib was totally eosinophilic. The typical findings of acute pancreatitis were not seen in the both group. By EM examination, zymogen granules (ZGs) of the sorafenib group spread into basal site of the acinar cells. ZGs mounted up on both of apical and baso-lateral plasma membrane and showed exocytosis. The levels of amylase mRNA were not elevated by sorafenib. In addition the expression of N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) proteins was not changed. Conclusions: The results suggest that the amount of acinar amylase production was not changed but the distribution of ZGs was altered by sorafenib. Sorafenib seemed to cause temporary loss of polarity of ZGs secretion in acinar cells by blocking apical exocytosis. Acute pancreatitis was not evident; thus the current model was not similar to the pancreatitis model caused by the supra-maximal secretagogue stimulation which blocks the apical exocytosis.


1976 ◽  
Vol 36 (2) ◽  
pp. 281-288
Author(s):  
U. R. Fölsch ◽  
K. G. Wormsley

1. The effect of a diet containing a trypsin inhibitor on the incorporation of radioactively labelled leucine into the pancreatic proteins secreted during stimulation with cholecystokinin-pancreozymin (CCK) was studied in rats.2. The total output of protein was significantly greater in the rats given raw soya-bean flour (RSF) compared with those given heat-inactivated soya-bean flour (HSF) (controls) in response to the sub- and supramaximal stimulation with CCK, but similar responses were obtained to maximal stimulation with CCK. Total protein output decreased continuously with time after reaching peak values at 90–120 min after the start of stimulation with CCK.3. The total output of radioactively labelled protein in RSF-fed rats was not different from that of the controls with sub- and supramaximal dose rats of CCK, but was significantly lower than that of the controls in response to the dose rate of CCK which produced maximal rates of pancreatic secretion.4. The specific activity of radioactively labelled protein increased continuously, while the output attained a constant rate during stimulation with all doses of CCK.5. We concluded that feeding the trypsin inhibitor-containing diet led to increased secretion of stored pancreatic protein, while secretion of newly synthesized protein was not altered. During the course of prolonged stimulation with CCK, irrespective of diet, there was increasing secretion of the newly synthesized protein compared with the pre-existing stored proteins of the pancreas, but it was unable to compensate for the decreased secretion of pre-formed protein.


1994 ◽  
Vol 72 (4) ◽  
pp. 533-544 ◽  
Author(s):  
Fatima Khalifa ◽  
Josiane Prost ◽  
Jacques Belleville ◽  
Louis Sarda

The time-course effects of two diets containing raw (RSF) or heated (HSF) soya-bean flour on the digestive enzyme levels in the pancreas and in pancreatic juice were investigated in growing rats fed, alternately, on RSF or HSF diets for two 4-week periods. These values were compared with those obtained in a control group fed on a casein diet. RSF and HSF diets lowered N balance (84.8 (SE 0.9), 82.6 (SE 0.8) and 79.9 (SE 0.8) % with control, HSF and RSF diets respectively, at the third week). However, they increased protease activities compared with the control diet (3-fold for trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) activities in pancreas contents and outputs with the RSF diet; 2-fold for trypsin in pancreas contents and outputs and by 60% for chymotrypsin contents with the HSF diet). The poorer nutritional N utilization might be attributable to soya-bean flour heat-stable (lectins) and heat-labile components (trypsin inhibitors). The decrease in lipid apparent digestibilities in RSF and HSF diets (97.0 (SE 0.8), 91.1 (SE 09) and 90.4 (SE 0.7) % with control, RSF and HSF diets at the seventh week) were correlated with a diminution in apparent lipase (EC 3,1.1.3; measured without addition of exogenous colipase), potential lipase (measured with addition of saturated amounts of exogenous colipase) and colipase activities. Compared with control values, gains in potential and apparent lipase outputs were diminished by nearly 40% and gain in colipase outputs by 60% with RSF and HSF diets. These results show clearly that heated or raw soya-bean flours have a significant inhibitory effect on lipase digestive enzyme activities in the pancreas and in its secretion, which might explain impaired lipid digestibility.


1979 ◽  
Vol 44 (10) ◽  
pp. 3177-3182 ◽  
Author(s):  
Mária Stančíková ◽  
Karel Trnavský

Cathepsin G was isolated from human polymorphonuclear leukocytes and purified by affinity chromatography on Antilysin-Sepharose column. Purified enzyme activated later collagenase isolated from leukocytes. Activation at 36°C was maximal after 30 min incubation. Inhibitors of cathepsin G - soya-bean trypsin inhibitor, diisopropyl phosphofluoridate and Antilysin were active in inhibiting the activation of latent collagenase by cathepsin G.


1963 ◽  
Vol 16 (1) ◽  
pp. 1-23 ◽  
Author(s):  
H. Warshawsky ◽  
C. P. Leblond ◽  
B. Droz

Radioautographs of pancreatic acinar cells were prepared in rats and mice sacrificed at various times after injection of leucine-, glycine-, or methionine-H3. Measurements of radioactivity concentration (number of silver grains per unit area) and relative protein concentration (by microspectrophotometry of Millon-treated sections) yielded the mean specific activity of proteins in various regions of the acinar cells. The 2 to 5 minute radioautographs as well as the specific activity time curves demonstrate protein synthesis in ergastoplasm. From there, most newly synthesized proteins migrate to and accumulate in the Golgi zone. Then they spread to the whole zymogen region and, finally, enter the excretory ducts. An attempt at estimating turnover times indicated that two classes of proteins are synthesized in the ergastoplasm: "sedentary" with a slow turnover (62.5 hours) and "exportable" with rapid turnover (4.7 minutes). It is estimated that the exportable proteins spend approximately 11.7 minutes in the Golgi zone where they are built up into zymogen granules, and thereafter 36.0 minutes as fully formed zymogen granules, before they are released outside the acinar cell as pancreatic secretion. The mean life span of a zymogen granule in the cell is estimated to be 47.7 minutes.


1946 ◽  
Vol 14 (3) ◽  
pp. 330-339 ◽  
Author(s):  
Kathleen M. Henry ◽  
S. K. Kon

1. The biological value of proteins at an 8% level of protein intake measured on rats by the method of Mitchell (7, 10) was 52 for white bread of 73% extraction, 76 for Cheddar cheese, 75 for a mixture of both foods when each supplied 50% of the protein, and 67 when the two sources of protein were given on alternate days. The true digestibilities were, respectively, 99, 100, 98 and 99.2. Similar experiments with dried skim milk and dried cooked potatoes yielded biological values of 71 for potato, 89 for milk, 86 for the mixture and 81 for the substances fed separately on alternate days. The true digestibilities were, respectively, 82, 90, 82 and 87.3. An attempt to carry out experiments of the same type with dried whey and dried potato failed because of deaths of some rats receiving the whey diet, probably because of its high content of lactose. A biological value of 76 was obtained for the potato proteins and of 70 for a mixture of whey and potato in which whey supplied 25% of the protein. The true digestibilities were, respectively, 82 and 68.4. The biological value and the true digestibility of the proteins of a sample of edible soya-bean flour were, respectively, 73 and 90.5. It is concluded that there is a marked supplementary relationship between the proteins of milk and potato and those of bread and cheese when the members of each pair supply equal amounts of protein and when they are given together. No supplementary relationship is exhibited when the sources of protein are given separately on alternate days.


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