Influence of bile salt molecular species on cholesterol crystallization from supersaturated model biles.

Time-sequential enzymatic determination of cholesterol (CH) crystals harvested by ultrafiltration, and concomitant polarizing light microscopy observations corroborated the striking importance of the bile salts (BS) species in determining CH crystals formation rate from supersaturated model biles incubated in vitro. The more hydrophilic tauroursodeoxycholate, taurohyocholate, glycohyocholate, taurohyodeoxycholate, glycohyodeoxycholate and glyco-3 alpha, hydroxy-6 oxo-5 beta-cholanate inhibited CH precipitation through the formation of a stabilized liquid-crystalline phase. In contrast, in all hydrophobic systems (taurine (T) and glycine (G) conjugates of cholate (C), deoxycholate (DC) and chenodeoxycholate (CDC)), CH crystals precipitated with time. When crystallized CH concentrations were plotted vs. time, the figures showed a sigmoidal pattern, consistent with the transition from metastable systems to stable equilibrium states. Over the equilibration period, the nucleation kinetics (as inferred from enzymatic measurements) and all crystallization events (as microscopically observed) were both shifted in time, depending on the BS species: they were earliest in CDC systems, then in DC systems, and finally in C systems. In the latter, the delay was clearly due to the formation of a transient labile liquid-crystalline phase. G-conjugation also induced a significant delay in CH precipitation, compared to T-conjugation. At last, maximum crystallized CH concentrations at equilibrium were in the decreasing order: C > CDC > DC and T-conjugates > G-homologues. All data are discussed in connection with BS hydrophobicities, with predictions from the phase equilibria of aqueous biliary lipid systems and with new insights into CH crystal habits.

Binding between immobilized anti-colipase purified antibodies and colipase. Radioimmunoassay of colipase from pig plasma and pancreatic juice.

Procedures for purification of porcine colipase II (Gly6-Gly89) and for obtaining purified anti-colipase antibodies are described. The interactions between antibodies immobilized on an Ultrogel AcA 22 column and colipase were investigated and colipase radioimmunoassay carried out. The immobilized antibody-colipase binding was preserved in the presence of mixed micelles, lipase, or both when added to the elution mixture. Bound colipase maintained its capability of interacting with mixed micelles, but not with lipase in either the presence or the absence of mixed micelles. It could be inferred that the antigenic site(s) is independent of the interfacial recognition site and close to the site of lipase recognition. Results are reported suggesting that one or both colipase histidyl residue-containing sequences are involved as antigenic determinant(s). Immunoreactive colipase, bound to a macromolecular protein complex, was found in the plasma of pig. This finding could be explained by an endocrine 'leakage' of colipase from the exocrine pancreatic cell rather than by passage through the intestinal mucosa.

Effect of beta-cyclodextrin dietary supplementation on biliary proteins and their resulting cholesterol nucleating activity in pigs.

We explored the possibility that the biliary protein fraction may support part of the variation in the nucleating activity previously measured in gallbladder biles of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to purify their total protein fraction. Proteins were quantified, and analysed through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay for albumin, and five putative effectors of cholesterol crystallisation, mucins, immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction. Each total protein fraction was also assayed for its ability to influence cholesterol precipitation, when added to supersaturated model bile. The current data provided evidence that the cholesterol crystallisation-promoting activity of biliary proteins in model biles increased with the beta-cyclodextrin dietary content. This occurred without any significant change in the total biliary protein content, but was associated with a significant decrease in the concentration of albumin and apolipoprotein A-I, resulting in changes in the overall balance of proteins in bile. Comparison of these results with the crystallisation figures previously obtained from the corresponding native biles led us to conclude that biliary proteins might influence the outcome of the crystallisation process, namely the final crystal concentration at equilibrium, but would not systematically represent a major driving force for determining the velocity of crystal formation in native bile of pigs.

Comparative apparent digestibility of casein in holoxenic, axenic, and Clostridium bifermentans monoassociated rats.

The aim of the present study was to determine the role of the intestinal microflora in the dietary utilization of casein. The apparent digestibility of dry matter, organic matter, energy, and nitrogen was measured in holoxenic, axenic, and Clostridium befermentans monoassociated rats deprived or not deprived of their pancreatic and bile secretions. The apparent digestibility of energy decreased in all the animals whatever the bacterial environment, after ligation of the common duct. Concerning the apparent digestibility of nitrogen, the intestinal microflora allowed the rats to compensate for the absence of the pancreatic proteolytic enzymes. It is suggested that a small part of casein, which was not hydrolyzed when the animals were deprived of their pancreatic and bile secretions, underwent a hydrolysis from the bacterial proteases.

Pharmacological and biochemical evidence for the simultaneous expression of CCKB/gastrin and CCKA receptors in the pig pancreas.

1. In the pig, the secretory response of the pancreas is not inhibited by the antagonist MK329 suggesting that cholecystokininA (CCKA) receptors are not involved. 2. Membranes were isolated from the pancreas of 6 Large White pigs to characterize their CCK receptors. 3. The binding of [125I]-BH-[Thr, Nle]CCK-9 was dependent on pH, maximal after a 90 min incubation period, saturable and reversible. Saturation analysis of the binding demonstrated a single class of high affinity sites (Kd = 0.22 +/- 0.02 nM) and a binding capacity, Bmax = 110.64 +/- 12.50 fmol mg-1 protein. 4. Competition binding by agonists and antagonists of CCKA and CCKB/gastrin receptors demonstrated the presence of two distinct binding components, sites presenting a high affinity for [Thr, Nle]CCK-9, gastrin, PD 135158, L-365, 260 and a low affinity for MK329, SR 27897, and sites presenting a high affinity for [Thr, Nle]CCK-9, MK329, SR 27897 and a low affinity for gastrin, PD 135158, L-365,260. 5. These pharmacological data demonstrate the presence of both CCKA and CCKB/gastrin receptors in the pig pancreas, the latter being predominant. 6. Two distinct membrane proteins (50 and 85-100 kDa, respectively) display pharmacological features of CCKB/gastrin and CCKA receptors. 7. In pigs, as in calves and humans, CCKB/gastrin receptors are predominant in the pancreas.

Effect of bombesin at low doses on the secretion of the exocrine pancreas and on plasma gastrin concentration in the conscious pig.

We investigated the role of low-doses of bombesin in the regulation of exocrine secretion in the pancreas of the conscious pig. In ten growing castrated male Large White pigs, bombesin was infused intravenously for 1 h at doses of 0 to 500 pmol/kg/h under a stimulation of secretin (36 pmol/kg/h). In six pigs, bombesin (50 pmol/kg/h) was administered alone for 2 h and its effect on pancreatic secretion was compared to that of an infusion of secretin. The pancreatic juice and the blood were collected at 15-min intervals for use in assays of protein in the juice and gastrin in the plasma. When bombesin was infused alone or in combination with secretin, the volume secreted was not altered. The protein output was not altered by secretin, but was increased by the infusion of bombesin, in a dose-dependent manner, reaching a plateau at 250 pmol/kg/h. The plasma gastrin levels were increased by bombesin, starting with the 50 pmol/kg/h dose. This effect was maximal at a dose of 100 pmol/kg/h. The levels remained below those measured after a standard meal, demonstrating that the effect of bombesin on the studied parameters is of physiological significance.

Effects of pancreatic polypeptide on the pancreatic exocrine secretion stimulated by secretin and cholecystokinin in the conscious pig.

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with pancreatic and duodenal fistulae for pancreatic secretion studies. Moreover, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Pancreatic juice was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8-day recovery period, perfusion studies were performed after an overnight fast. After a 30-min basal period, sustained pancreatic flow and protein output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin + CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Neither pancreatic flow nor bicarbonate output were affected whatever the dose of infused PP. On the contrary, protein concentration and output decreased with the lowest dose of PP (200 pmol/kg/h) and the diminution was more pronounced with the other doses. With 600 pmol/kg/h as well as with 800 and 1200 pmol/kg/h of PP, pancreatic protein output fell to about 20% of values obtained with secretin + CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Protein concentration and output returned to values obtained with secretin + CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases pancreatic protein output whereas pancreatic flow remains unaffected.

Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig.

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected.

Early adaptation of pancreas to a protein-enriched diet: role of cholecystokinin and gastrin-releasing peptide.

Feeding rats a diet containing high levels of protein (as casein) increases the secretion and biosynthesis of pancreatic serine proteases. Cholecystokinin (CCK) presumably plays a role in this process although other GI peptides such as the gastrin-releasing peptide (GRP) may be involved. In this article, we describe the kinetics of pancreatic adaptation to a diet containing 45% protein as soybean and fish. Then we report the effect of treatment with either a cholecystokinin-receptor antagonist (MK-329) or a gastrin-releasing peptide-receptor antagonist ([D-F5 Phe6, D-Ala11]-Bn(6-13)OMe, or BIM 26226) on pancreatic adaptation to this diet. Prior to experiments, adult male Fischer rats received a diet containing 22% protein for 1 week. In the first experiment, 48 rats were fed a diet containing 45% protein; they were killed after 0-7 days. In the second experiment, 53 rats were fed the 22- or 45%-protein diet and received three daily injections of either the vehicle alone, MK-329, or BIM 26226 for 7 days before they were killed. When the protein-rich diet was fed for 0-7 days, amylase, in vitro biosynthesis, and mRNA levels were gradually decreased while serine protease biosynthesis was increased, reflecting the general enhancement of chymotrypsinogen, trypsinogen, and elastase mRNA levels. For all these parameters, adaptation leveled off after a 5-day feeding. When the protein diets were fed for 7 days, MK-329 significantly inhibited the adaptation of trypsin (specific activity and mRNA) and elastase (mRNAs) to the 45%-protein diet. BIM 26226 had no effect on pancreatic adaptation to the protein-rich diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of CCK in the regulation of secretion and adaptation in the pig pancreas.

The effect of cholecystokinin (CCK) on the pancreas was investigated in the pig in two experiments. Fifteen pigs were fed a diet containing 17 or 48% protein with or without MK329 (4.5 mg per meal). MK329 enhanced the postprandial peak of plasma CCK during the first 30 min, but pancreas adaptation to high protein was not affected. Sixteen pigs were divided into two groups: 12 pigs were infused with CCK-8 + secretin for 1 h and four pigs received a standard meal. In both groups, pancreatic secretion tests were performed under infusion of the vehicle alone or with MK329. After CCK + secretin, MK329 (65-500 micrograms/kg/h) did not alter CCK plasma levels and reduced the early pancreatic protein response by about 30%. Enzyme outputs in pancreatic juice were modestly affected by MK329. After the meal, MK329 (500 micrograms/kg/h) doubled the postprandial peak of plasma CCK and lowered the pancreatic protein output by 35-40% for the first 30 min. We suggest that (a) pancreatic adaptation to high dietary protein is not mediated via CCK-A receptors and (b) the stimulation of pancreatic protein secretion by a meal or by exogenous CCK-8 is mediated partly by CCK-A receptors.

Plasma neurotensin in the conscious pig: release by individual food components and effects on exocrine pancreas secretion.

In conscious pigs, i.v. infusion of serial doses of neurotensin (NT, actual doses of 0.24-59.4 pmol.kg-1.min-1) on a background of secretin resulted in a linear increase of plasma NT-like immunoreactivity (NT-LI), as measured with an antiserum that requires the biologically active C-terminal part of the molecule for recognition. The NT infusions were accompanied by a dose-related increase of pancreatic volume and bicarbonate and protein output. The threshold plasma NT-LI concentrations for significant increases of pancreatic enzymes and of pancreatic fluid and bicarbonate were 46.6 +/- 7.0 and 161.3 +/- 10.8 pM, respectively. Food intake was followed by a sharp pancreatic response and a progressive increase of plasma NT-LI level to a peak of about 27.7 +/- 3.0 pM from the basal level 11.8 +/- 1.6 pM. The carbohydrate fraction of the meal was predominantly responsible for the NT release observed after meal intake. High-performance liquid chromatography analysis of plasma samples collected during NT infusion or after meal ingestion revealed one immunoreactive peak coeluting with intact NT. Pancreatic polypeptide was released on infusion of high, supraphysiological doses of NT, while plasma somatostatin remained at low basal values. It is concluded that in the pig, intact NT is released after a standard meal predominantly through the carbohydrate fraction of the diet, NT is a stimulant of exocrine pancreas secretion, and the modest pancreatic response to physiologic increments of plasma NT-LI on peptide infusion is not attributable to indirect inhibition of the exocrine pancreas by NT-released pancreatic polypeptide or somatostatin.

Modulation of pancreatic secretion by capsaicin-sensitive sensory neurons in the rat.

The purpose of this work was to study whether stimulation or destruction of sensory afferents can modulate pancreatic secretion. The neurotoxin capsaicin is specific for a subpopulation of small diameter primary afferent neurons. Small doses of capsaicin were administered to anesthetized rats as intraduodenal or intragastric bolus injections to stimulate digestive sensory fibers, and pancreatic secretory response was measured. In addition, several high-dose subcutaneous capsaicin injections were administered 10 days before the experiments began, in order to inactivate sensory fibers. Basal and 2-deoxy-D-glucose (2DG)-stimulated pancreatic secretion was then measured. Intraduodenal capsaicin (96-3,050 micrograms/kg) induced a progressive (peak response 40-60 min after the injection), dose-related and long-lasting (> 180 min) increase in pancreatic output of sodium, bicarbonate, and total protein. The maximal response was obtained with 964 micrograms/kg capsaicin; it amounted to about 15% of the maximal response to exogenous cholecystokinin octapeptide (CCK8). The response was not decreased by atropine, hexamethonium, vagotomy, a mixture of adrenoceptor antagonists (prazosin + idazoxan + propranolol), or by the CCKB receptor antagonist L365,260. In contrast, the CCKA receptor antagonist L364,718 reduced by 30-40% the sodium and bicarbonate response and reduced by 90% the protein response induced by capsaicin, but not the response induced by methacholine or 2DG. However, intraluminal capsaicin did not release CCK in a preparation of isolated perfused duodeno-jejunum. Intragastric capsaicin did not significantly change pancreatic secretion. Capsaicin pretreatment had no effect on basal and 2DG-stimulated secretion, but abolished the response to intraduodenal capsaicin. In conclusion, intraduodenal capsaicin can stimulate external pancreatic secretion in anesthetized rats through capsaicin-sensitive sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of digestive enzymes in the piglet from birth to 8 weeks. II. Intestine and intestinal disaccharidases.

The changes with age of intestinal mucosa, protein, lactase, maltase and sucrase were followed in the piglet between day 105 of gestation and 8 weeks after birth. Lactase and maltase activities appeared during fetal life in the whole of the small intestine. Activity of sucrase was recorded after the 1st postnatal week. Lactase activity was high at birth and reached a maximum at 1 week (X 2.5); maltase activity which was low at birth increased to the 8th week (X 143). Activities of all enzymes were low in the duodenum; lactase was most active in the jejumum. Similar activities of maltase and sucrase were found in the two distal parts of the small intestine. Specific activity (related to protein content) of lactase reached a maximum at the end of the 1st week after birth and decreased afterwards. Specific maltase and sucrase activities were higher in the 2nd week, decreased between the 2nd and 4th week and increased afterwards (maltase) or decreased to the 6th--8th week (sucrase).

Development of digestive enzymes in the piglet from birth to 8 weeks. I. Pancreas and pancreatic enzymes.

The development of pancreatic tissue (fresh weight, total proteins, RNA and DNA) and of the level of pancreatic enzymes (trypsin, chymotrypsin, lipase and amylase) of the piglet has been followed from birth to the age of 8 weeks in 10 animals at each of 7 stages. There was an increase with age and body weight of the total fresh weight of the exocrine pancreas. From birth until 4 weeks the development of the pancreatic gland was due to hyperplasia; from the 4th week till the 8th week of age, it was due both to hyperplasia and hypertrophy. There was a specific period, at the age of 3--4 weeks, from which total enzymatic activities markedly increased. Furthermore, from the 4th week of age there was a rise in the intake of total dietary proteins, fat and carbohydrates, due to the intake of solid food.

Ion-pair high-performance liquid chromatography of bile salt conjugates: application to pig bile.

The high-performance liquid chromatographic separation and quantitation of conjugated bile salts from pig bile is reported. Synthetic standards and bile samples were chromatographed on a C18 reversed phase column using acetonitrile/water/tetrabutyl ammonium phosphate as an isocratic mobile phase at a flow rate of 1 mL/min. Detection of the ion-pairs was at 214 nm. The method permits efficient separation of all conjugated pig biliary bile salts without prior modification or treatment of the samples. Analysis of 12 pig biles showed that 85% of the bile salts are conjugated to glycine. The three main conjugated bile salts were glyco-3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid (GHC), glyco-3 alpha,7 alpha-dihydroxy-5 beta-cholanoic acid (GCDC), and glyco-3 alpha,6 alpha-dihydroxy-5 beta-cholanoic acid (GHDC). Glyco-3 alpha-hydroxy-6-oxo-5 beta-cholanoic acid (G3 alpha 6oxo), tauro-3 alpha,7 alpha-dihydroxy-5 beta-cholanoic acid (TCDC), tauro-3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid (THC), and tauro-3 alpha,6 alpha-dihydroxy-5 beta-cholanoic acid (THDC) were found to contribute each for 4 to 5% to the total. An excellent correlation was found between the sum of conjugated bile salts quantitated by high-performance liquid chromatography (HPLC) and values obtained by conventional enzymatic assay. Simplicity, efficiency and relative rapidity of the method render it suitable for routine analyses.

[Endo-surgical dissection of the upper urinary tract through the retroperitoneal and transperitoneal route: an experimental study with pigs and cadavers]. / Dissection endo-chirurgicale du haut appareil urinaire par voie rétropéritonéale et transpéritonéale: une étude expérimentale chez le cochon et chez le cadavre.

In order to define the best method for endosurgical dissection of the upper urinary tract, an experimental study comparing the retroperitoneal and transperitoneal approaches was performed. Between September 1991 and February 1992, 15 female pigs and 8 human cadavres underwent endosurgical dissection of the upper urinary tract. The retroperitoneal approach was used in 8 pigs and 5 cadavres. In the lateral supine position, the retroperitoneum was insufflated at the lower pole of the kidney, via a 2 cm cutaneo-muscular incision, followed by a blind dissection with the finger to create a space in the retroperitoneal fat. Four trocars were inserted into the retroperitoneal space allowing dissection of the ureter, kidney and its vascular pedicle. The renal vessels and the ureter were then clipped or stapled with the endo-GIA then sectioned. The operation was successfully performed in all of the pigs with a mean operating time of 2 hours. Complications were limited to two peritoneal effractions. Retroperitoneal endosurgical dissection was much longer and more difficult to perform on the cadavre (mean operating time: 3 hours). Satisfactory retropneumoperitoneum was never able to be obtained due to the large amount of retroperitoneal fat and the proximity of the twelfth rib and posterior iliac crest interfered with the insertion of the trocars and made dissection more difficult. The transperitoneal approach was performed in 7 pigs and three cadavres. In the lateral supine position, after creating pneumoperitoneum using a Veress needle, 4 trocars were inserted into the peritoneal cavity. Toldt's fascia was gripped and incised allowing retraction of the colon towards the midline, thereby exposing the renal region. The ureter and the renal vessels were dissected. The renal artery and vein were then clipped or stapled with the endo-GIA then sectioned, while the ureter was clipped and sectioned. The complications of the transperitoneal route were: an injury to the small intestine during insertion of a trocar and haemorrhage due to accidental section of a lower pole renal artery, which was able to be controlled by application of clips. In the pig, the transperitoneal approach was as simple to perform as the retroperitoneal approach and the mean operating time was the same (two hours).(ABSTRACT TRUNCATED AT 400 WORDS)

The adaptation of digestive enzymes to the diet: its physiological significance.

Digestive enzymes adapt to the diet when substrate intake is altered. An analysis of experimental works shows that this process includes many enzymes. The intestinal step of digestion is the most important in the enzyme breakdown of dietary components. In the first part of this paper, I have pooled the data on the adaptive potency of pancreatic and intestinal enzymes. When protein, carbohydrate and lipid digestions are considered successively, it is clear that the enzymes involved adapt to any change in substrate intake. For instance, when the amount of starch intake increases, the specific activity of pancreatic amylase is stimulated. At the same time, augmenting the disaccharide level leads to an increase in specific disaccharidase activity, and the absorption rate of some simple hydrolytic products, such as fructose, increases. It thus appears that altering the amount of starch intake leads to a parallel change in the activity of all the enzymes involved in the sequential hydrolysis of the dietary carbohydrates. The second part of the paper discusses the physiological significance of this adaptation in terms of utility to the animal. Two situations are considered in which (i) the nutritional requirements are supplied by food or (ii) they are not supplied either because of a dietary or an enzyme deficiency. When the nutritional requirements, particularly that of protein, are met, adaptation is apparently not useful to the animal. Nevertheless, the role of this adaptation on the hydrolysis rate of different substrates can be supposed. When nutritional requirements are not met, some data show that enzyme adaptation may be advantageous to the animal. If dietary restriction is not too severe and thus the biosynthesis of all the enzymes markedly decreases, then digestive secretions would export considerable nitrogenous material into the gastrointestinal lumen; this material could be a substrate compensating for the essential components lacking in the diet. Any enzyme deficiency leading to substrate decrease is similar to a dietary deficiency. Many experimental studies have shown that in pancreatic deficiency the adaptive potency of the organism is responsible for establishing digestive compensation.

Exclusion of pancreatic exocrine secretion from intestine in the pig: existence of a digestive compensation.

The apparent digestibility of a diet was studied over a period of 87 days after ligature of the pancreatic duct, in the growing pig. Sham operated pigs were used as controls. Feces and urine collections were made during three periods of 10 days each. Mean daily gain of sham operated pigs was higher (560 g/day) than that of pancreatic duct ligated pigs (421 g/day), throughout the experiment. Within the first period (15-24 days after ligature), the apparent digestibility of nitrogen was most affected (-35.6%) while that of energy decreased by 12.1% as compared to values obtained in sham operated pigs. Nitrogen retention was similar in all pigs. Between the 1st (15-25 days) and the 3rd period (78-87 days) after exclusion of the pancreatic secretion from intestine, the apparent digestibility of nitrogen increased by 20% and that of energy by 6%, which might suggest digestive compensation. At the end of the experiment, weights of empty small intestine and liver were significantly higher in the pancreatic duct ligated pigs. The origin of the digestive compensation is discussed.