Effect of pectin on the function of the rat exocrine pancreas

The author studied the effect of three weeks' administration of a 5% pectin concentration in the standard (Larsen) diet on basal and cholecystokinin octapeptide-(CCK8-) stimulated pancreatic exosecretion in rats. Protein, amylase and trypsinogen output determined in pancreatic juice obtained under basal conditions and after CCK8 stimulation of the exocrine pancreas showed no statistically significant differences between rats fed on the standard and the pectin-enriched Larsen diet. Our observations and studies by other authors show that the direct effect of dietary fibre on the exocrine function of the pancreas is an open question as far as further research is concerned.     

Protective effect of long term high fiber diet consumption on rat exocrine pancreatic function after chronic ethanol intake

The effects of ethanol administration on exocrine pancreas have been widely studied, but little is known about the effect of dietary fiber in combination with chronic ethanol on exocrine pancreatic function. The aim of this work was to examine the chronic effects of a high fiber diet, ethanol ingestion, and a combination of both on the function of the rat exocrine pancreas. Four groups of rats were fed for six months the following diets: 1.- NW: standard laboratory diet; 2.- FW: high fiber diet (15% cellulose); 3.- NE: standard laboratory diet and 20% ethanol in the drinking water; and 4.- FE: high fiber diet and 20% ethanol. Cholecystokinin (CCK) and acetylcholine (Ach) effects on amylase release and intracellular calcium mobilization in pancreatic acini were studied. In rats fed a 20% ethanol (NE), both the basal amylase release and the basal [Ca(2+)](i) were significantly increased; nonetheless, CCK and Ach-induced amylase release were significantly reduced compared with control rats. Ach- but not CCK-stimulated [Ca(2+)](i) increase in NE rats was significantly decreased compared with NW. In rats fed a combination of ethanol and a high fiber diet (FE) all the parameters under study were not significantly affected compared to control rats (NW). In conclusion, high fiber consumption does not alter the function of the exocrine pancreas. However, it ameliorates the deleterious effect of chronic ethanol consumption on pancreatic amylase secretion and, at least partially, reverses the ethanol-induced alterations on [Ca(2+)](i) in the rat exocrine pancreas.     

Effect of dietary fat on pancreatic lipase levels in the rat

The effect of dietary fat on levels of lipase and other enzymes in rat pancreas has been studied. It was possible to raise levels of lipase in animals by supplementing their commercial chow diet with added fat or by raising the level of fat in semipurified diets from 4% to 22%. Pancreatic amylase levels decreased in rats fed the high fat diets, whereas levels of chymotrypsinogen and trypsinogen were unaffected. The type of carbohydrate in the semipurified diets made no difference. Thus, the levels of enzymes in rats fed dextrose-containing diets or cornstarch-containing diets were similar. On the basis of the present data, and results of others, it would appear that levels of pancreatic lipase are increased when the fat content of the diet is raised from about 5% to 15-22%, but that little or no additional increase in lipase levels can be attained by any further increase in the amount of dietary fat.     

Effects of inverse changes in dietary lipid and carbohydrate on the synthesis of some pancreatic secretory proteins

The effect of ingesting isocaloric and isonitrogenous diets with increasing amounts of lipid (0-30%) and consequently decreasing amounts of carbohydrates (68.7-1.25%) on the exocrine pancreas was studied in adult male Wistar rats. Pancreatic contents of chymotrypsin, lipase and colipase activity, as well as synthesis of amylase, lipase, procarboxypeptidases and individual serine proteases were examined. Lipid-free diets and diets containing 1% lipid were found to have little effect on pancreatic proteins as compared with lipid-rich diets where two distinct patterns of response were observed. Ingestion of diets containing 3-20% lipid resulted in a progressive increase in the activity of lipase, colipase and chymotrypsin up to 2-fold in the first case and 1.6-fold in the two other cases when animals were fed the 20% fat diet. Under the latter conditions, the relative synthesis of secretory proteins, as expressed as percentage of the radioactivity incorporated into individual proteins compared to that incorporated into the total mixture of exocrine proteins, was unchanged for procarboxypeptidases, whereas it was stimulated for lipase (2-fold) and serine proteases (1.6-fold). Amylase relative synthesis progressively decreased as the lipid content of diets increased. Consumption of hyperlipidic diets containing 25% and 30% fat resulted in a further enhancement in the activity of lipase and colipase in the gland in contrast with chymotrypsin activity which was unchanged as compared to the control diet (3% lipid). As far as biosynthesis was concerned, a plateau in the relative synthesis of lipase and serine protease was reached. Amylase relative synthesis further decreased down to 2.2-fold when rats were fed the 30% fat-rich diet whereas that of procarboxypeptidases was markedly increased (about 1.7-fold). Absolute rates of synthesis of total pancreatic secretory proteins, as expressed with regard to the DNA content of the tissue, indicated that biosynthesis of all secretory pancreatic proteins was stimulated by hyperlipidic diets (at least 2-fold with the 30% lipid diet). Consequently, when such an increase was taken into consideration, the absolute synthesis of amylase was found to be unchanged throughout the dietary manipulations, whereas that of lipase, procarboxypeptidases and serine proteases were stimulated by 4.0-fold, 3.4-fold and 3.2-fold, respectively.     

Responses of the exocrine pancreatic secretion to spontaneous feeding in rats with bile-pancreatic juice diversion

The regulatory response of the exocrine pancreas was examined in rats under unanesthetized and unrestrained conditions. The previous study demonstrated that the pancreatic protease secretion increased 2-fold after spontaneous feeding of a low protein diet in chronically bile-pancreatic cannulated rats (normal rats) whose bile-pancreatic juice (BPJ) was returned to the duodenum. In the present study, we observed the response of the exocrine pancreatic secretion to spontaneous feeding of a low protein diet in rats with chronic diversion of BPJ from the proximal small intestine for 6 days (bypass rat) whose diverted BPJ was returned to the upper ileum. During BPJ diversion, the dry weight and the protein content of the pancreas were increased 2-fold, compared with normal rats. Also, the levels of trypsinogen and chymotrypsinogen in the pancreas were increased several times, but amylase was decreased. The basal secretion of enzymes after a 24-hr fast was enhanced in bypass rats in proportion to the pancreatic enzyme contents. After spontaneous feeding of 8% casein fat-free diet, the increases in the pancreatic secretion of bypass rats were much smaller than those of normal rats. In contrast, the increase of BPJ flow of bypass rats after feeding was greater than that of normal rats. These findings represent that the chronic diversion of BPJ exerts hypergrowth of pancreas and hypersecretion of proteases in the fasting state, and less sensitivity of pancreatic enzyme secretion to dietary feeding.     

Pancreatic exocrine secretion in the pig following test meals of different composition and intra-duodenal loads of glucose and maltose.

Eleven pigs were fitted with pancreatic and duodenal fistulae, and pancreatic juice collected permanently. Amylase, chymotrypsin, lipase and total proteins were determined in juice collected within 2 and 6 hours after different test-meals or intraduodenal loads of glucose and maltose. In the pancreatic juice of pigs adapted to a high-lipid diet and submitted to a high-carbohydrate test-meal the activity of amylase was increased by 50%. When the consumption of the high-lipid meal was associated with an intraduodenal load of 100 g of glucose all the enzyme activities were stimulated when compared to the effect of meal alone, but only the activity of amylase was significantly increased (+ 82%). In the juice of pigs adapted to a balanced diet and submitted to intraduodenal loads of 150 ml of water, 50 g of glucose, 50 g of maltose and 150 g of maltose, the enzyme activities remained almost constant with the load of water and 50 g of maltose but with 50 g of glucose and 150 g of maltose loads, amylase activity was increased by 20% and 30% respectively. It is suggested, that the exocrine pancreas of the pig adapts itself rapidly to the changes in the size of the intestinal pool of starch hydrolysis products.     

Inhibitory effect of pancreastatin on pancreatic exocrine secretion in the conscious rat

The effect of newly discovered pancreastatin on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine was examined in the conscious rat. Exogenous pancreastatin infusion (20, 100 and 200 pmol/kg.h) inhibited pancreatic protein and fluid outputs during BPJ diversion in a dose-dependent manner. Pancreastatin did not affect plasma cholecystokinin (CCK) concentrations. Pancreastatin (100 pmol/kg.h) inhibited CCK-stimulated pancreatic secretion, but did not inhibit secretin-stimulated pancreatic secretion. Pancreastatin alone, however, did not affect basal pancreatic secretion. In contrast, pancreastatin (10(-10)-10(-7)M) did not suppress CCK-stimulated amylase release from isolated rat pancreatic acini. These results indicate that pancreastatin has an inhibitory action on exocrine function of the pancreas. This action may not be mediated by direct mechanisms and nor via an inhibition of CCK release. It is suggested that pancreastatin may play a role in the regulation of the intestinal phase of exocrine pancreatic secretion.     

Response of exocrine pancreas to corticosterone and aldosterone after adrenalectomy

The long-term effect of adrenalectomy (Adx) on the exocrine pancreas was examined in female adult rats. Pancreatic amylase concentration decrease to 50% of the control level starting 10 days after Adx, whereas the levels of trypsinogen and lipase remained unchanged. Replacement studies beginning 24 h after surgery with corticosterone (B, 1 mg/100 g body wt) or aldosterone (ALDO, 8 micrograms/100 g body wt) alone did not prevent the decline in amylase after Adx. However, when both hormones were administered together, pancreatic amylase concentration was maintained at a level similar to that of the control group. Serum corticosterone levels in the rats receiving B alone or B + ALDO were not different, and were comparable to levels found in normal rats. Both ALDO and B, given for 5 days starting 10 days after Adx, were required to restore amylase concentrations toward control values. When spironolactone (SPIRO, 3 mg/100 g body wt), a specific mineralocorticoid receptor blocker was administered bid together with ALDO + B, it blocked the increase in pancreatic amylase seen in ALDO + B treated rats but did not affect the serum corticosterone levels. These results suggest that mineralocorticoids are also involved in modulating the level of amylase in the rat exocrine pancreas.     

Recovery of exocrine pancreas six months following pancreatitis induction with L-arginine in streptozotocin-diabetic rats.

The aim of the present work was to investigate the laboratory and morphologic alterations in the pancreas 6 months after pancreatitis induction with L-arginine (Arg) in normal and streptozotocin (STZ)-diabetic rats. The amylase content of the pancreas was significantly decreased in the Arg-treated groups vs. the control group. No significant changes were observed in the DNA, soluble protein and lipase contents of the pancreas. In the STZ-treated groups, the serum glucose level was significantly elevated, whereas the serum immunoreactive insulin (IRI) level was significantly decreased vs. the control group. In these treated groups, the amylase content of the pancreas was also significantly decreased, but that of trypsinogen was significantly elevated vs. the control group. Histologic sections revealed periductal fibroses, adipose tissue and tubular complexes in the Arg-treated rats, but centroacinar hyperplasia was not observed in these groups. No alterations were observed on histological examination in the diabetic rats vs. normal rats 6 months following pancreatitis induction. In conclusion, a major restitution of the pancreatic enzyme content, but moderate histologic alterations were detected 6 months following pancreatitis induction with Arg. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this long-term study, but not to modify the recovery of the exocrine pancreas 6 months following Arg-induced pancreatitis.     

The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin,secretin and cholecystokinin in growing pigs

The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T‐shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered.

Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and a‐amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.V. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.     

Pancreatic adaptation to dietary lipids is mediated by changes in lipase mRNA

Lipase activity, rates of biosynthesis of lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) and amylase (1,4-alpha-D-glucan glucanohydrolase, EC 3.2.1.1) as well as concentrations of their corresponding mRNAs were measured in the pancreatic tissue of rats fed isocaloric and isoprotein diets with inverse changes in the amounts of lipids and carbohydrates. A control diet (3% sunflower oil--62% starch) and three lipid-rich diets (10% sunflower oil--46.2% starch, 25% sunflower oil--12.5% starch and 30% sunflower oil--1.25% starch) were fed to rats for 10 days. Ingestion of the 10% lipid diet already resulted in a 1.4-fold increase in lipase activity while a 2.4-fold increase was observed with the other 2 high-lipid low-carbohydrate diets. Similarly, 1.3- and 3.1-fold increases in the total rate of protein synthesis were measured in pancreatic lobules of rats fed 10 and 25% or 30% lipid diets, respectively, as compared with control animals. While absolute lipase synthesis showed an important increase during the dietary manipulation (1.7- and 5.9-fold, respectively), amylase synthesis was significantly lower (1.1- and 1.5-fold, respectively). The level of lipase mRNA, as measured by dot-blot hybridization with the corresponding specific cDNA, showed a 2.2-fold increase (10% lipid diet) and a 3.9-fold increase (25% lipid diet), whereas the level of amylase mRNA showed only 1.1- and 1.3-fold increases under the same experimental conditions. These data demonstrated that protein-specific synthesis rates more accurately reflected pancreatic adaptive states than tissue levels of enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical changes in the exocrine pancreas of rats fed caffeine

Coffee consumption has been associated with pancreatic disorders, but the mechanisms involved remain to be elucidated. This investigation examines the effects of caffeine consumption on the structure and function of the exocrine pancreas. Groups of rats, fed ad libitum commercial laboratory diet, were given drinking water which contained either caffeine (0.09 mg/ml) or nothing at all. The rats were allowed drink ad libitum and were killed 6 weeks later. Final body and pancreatic weights were not significantly different between the groups at the end of the experimental period. Although no ultrastructural effects of caffeine on the pancreas were observed, amylase and trypsinogen activity was 35% higher in pancreatic homogenates from caffeine-fed rats compared with controls. In addition, levels of immunoreactive cationic trypsin(ogen) were 41% higher than control levels in pancreases from the caffeine-fed rats. Also, the circulating levels of amylase and immunoreactive cationic trypsin(ogen) in serum were lower in the caffeine group compared with controls. When dispersed pancreatic acini isolated from the caffeine-fed rats were incubated in vitro with increasing concentrations of CCK-8 or nicotine, the rate of release of amylase, trypsinogen, and chymotrypsinogen was lower than in the control rats. This effect did not appear to be due to inhibition of protein synthesis, as determined by [3H]leucine incorporation into acinar protein. These data suggest that prolonged intake of caffeine at common dietary levels inhibits pancreatic enzyme secretion.     

Effects of diet and age on lipoprotein lipase and hepatic triglyceride lipase activities in the rat

Plasma clearance of triglyceride-rich lipoproteins appears decreased in aged humans and rats and may be due to lowered activities of the lipases responsible for lipid degradation. This study was designed to examine differential effects of age and diet on lipoprotein lipase (LPL) activity of adipose and heart tissue and hepatic triglyceride lipase (HTGL) activity. LPL and HTGL activities were examined in 3- and 13-month-old Sprague-Dawley rats after they had consumed either a high-carbohydrate or a high-fat diet for 14 days. The data were analyzed for age and diet differences by two-way analysis of variance. Although animals in the two age groups consumed diets of equal caloric content, the older rats gained less weight. Rats on the high-carbohydrate diet consumed less calories and gained less weight than the fat fed rats in both age groups. Neither heart nor adipose tissue LPL activity differed when examined for age or diet. HTGL activity levels, while not affected by age, were higher in the carbohydrate fed rats (P = 0.014). Regardless of age group, fasting plasma cholesterol levels were significantly higher in the carbohydrate-fed rats than fat-fed rats (P = 0.002). Thus, the diet effect was much stronger than the age effect for HTGL and plasma cholesterol levels.     

Evidence for several storage and exportation pathways of pancreatic digestive enzymes during protein malnutrition followed by refeeding

Outputs of pancreatic juice hydrolase were constant during a three-hour collection in control rats fed 20% protein and in malnourished rats fed on a low protein diet (5% protein). However, during the same time after a 3H-Leucine pulse, the relative proportion of each labelled enzyme (newly synthesized) were changed. In control rats, this phenomenon was specially obvious for trypsinogen 2 (Tg2) and chymotrypsinogen 1 (Chtg1), and support the existence of separate pools for various pancreatic hydrolases. In malnourished rats, the relative proportion of labelled Tg2 is not modified by protein malnutrition, whereas the proportion of labelled amylase, lipase and Chtg1 were decreased. Refeeding carried out the same labelling profile of each enzyme in the two groups.     

Pancreatic hydrolases in cold-induced hyperphagia of rats fed a low or high-fat diet

Rats fed either a low (2p. 100) or high (40 p. 100)-fat diet were exposed to 22 or 5 degrees C. The resulting hyperphagia adequately compensated energy losses as judged from body weight. The cold-induced hyperphagia was accompanied by a non-parallel increase in pancreatic hydrolases. Amylase and lipase were not increased above the adaptive levels they had respectively reached in the heat with a high-starch or high-lipid diet. Chymotrypsinogen, on the contrary, responded to increased intake of both diets. It also responded to the higher protein concentration in the high-fat diet caused by isocaloric replacement of starch by fat. Colipase varied independently of lipase and was increased additively by fat and protein intakes. Consequently, although limiting for lipase in the warm, colipase rose to a 1:1 ratio in the cold. Increased intake had a consistent pleiotropic effect evidenced by an increase of amylase with the high-fat diet and of lipase with the low-fat diet. The net effect was a significant increase in the lipid-digesting potential of the organism of lipid-fed animals upon exposure to cold, while the starch-digesting potential remained unaffected in starch-fed animals.     

Effects of diets rich in triglycerides and phospholipids on lipase and phospholipase A activities in rat pancreatic juice and pancreas]

Lipase and phospholipase A activities were increased in the pancreas and pancreatic juice of rats ingesting during two months 20% phospholipids- or triglycerides-rich diets. The activity of lipase is higher with the triglycerides-rich diet and the phospholipase A activity is higher with the phospholipids-rich diet. After seven days of the experiment, these two enzymes activities were less increased with diet containing 40% lipids.     

Nonparallel secretion of enzymes by the rabbit pancreas

Since nonparallel secretion of enzymes by the exocrine pancreas has been demonstrated with several experimental models, we were interested in verifying a recent claim that enzyme secretion remained strictly proportional (parallel) upon stimulation of the in vivo rabbit pancreas. Pancreatic juice was collected by extraduodenal cannulation of the pancreatic duct, in two different protocols. In the first protocol the administration of pentobarbital induces a mild anesthesia. Under this condition, amylase and chymotrypsin secretion remained parallel after cholecystokinin stimulation. In a second protocol, a deeper and constant anesthesia was attained with Fluothane resulting in a lower basal protein output than in the first protocol. Pancreatic secretion was collected under intravenous secretin perfusion (4.5 clinical units X kg-1 X h-1). After stabilization and basal collection periods, pancreatic secretion was stimulated with an i.v. bolus injection of either cholecystokinin (2 Ivy dog units/kg), caerulein (0.1 micrograms/kg), or carbachol (6 micrograms/kg). Upon stimulation of the pancreas, protein output increased an average of 30-fold and there was a concomitant 20-25% decrease in the ratio of the specific activities of amylase to chymotrypsin which resulted from a greater increase in the specific activity of chymotrypsin in pancreatic juice after stimulation of secretion. Thus, under appropriate conditions, nonparallel secretion of enzymes by the exocrine pancreas can be demonstrated in yet another experimental model. Furthermore, the proportion of amylase and chymotrypsin activities in pancreatic juice are once more shown to be dependent, up to a threshold, upon the rate of protein output by this exocrine gland.     

Neurotensin modulates the composition of pancreatic exocrine secretions in chickens

The effects of neurotensin on pancreatic exocrine secretion were examined in fasted, conscious White Leghorn hens. A cannula was surgically implanted in the central duct serving the ventral lobe of the pancreas in order to collect pure pancreatic juice. Following recovery, neurotensin was infused intravenously at 3.6 or 10.8 pmol/kg*min. The volume and pH of the pancreatic secretions were recorded and total pancreatic protein concentration, amylase, lipase, trypsin, and chymotrypsin activity were measured every 30 min for 2 hr and compared to secretions following the infusion of 0.9% saline. Our results demonstrated that neurotensin did not affect the pH nor the pancreatic juice protein concentration, but did increase secretion rate following neurotensin infusion at 3.6 pmol/kg*min. Amylase activity was significantly depressed during neurotensin infusions, while lipase (both pancreatic and carboxylester lipase) activity was significantly elevated. The ratio of amylase to lipase activity was especially depressed by neurotensin infusion at 10.8 pmol/kg*min. Insufficient secretory activity prevented a balanced statistical analysis of chymotrypsin activity, but from a pooled analysis, neurotensin had no effect on protease activity in the pancreatic juice. These results support our current research indicating that neurotensin may be a hormonal regulator of postprandial lipid digestion in chickens.     

Expression of amylase and other pancreatic genes in Xenopus

To better understand the relationship between the endocrine and exocrine cell types in the Xenopus pancreas, we have cloned the Xenopus amylase cDNA and compared its expression profile with that of four other pancreatic markers: insulin, glucagon, elastase and trypsinogen. Our results demonstrate that the first pancreatic marker to be expressed is insulin, exclusively in the dorsal pancreas. These insulin-expressing cells form small groups which resemble islets, but no insulin is detected in the ventral pancreas until stage 47. In contrast, the exocrine markers, amylase, elastase and trypsinogen are first expressed only in the ventral pancreas beginning at stage 41; by stage 45 their expression extends into the dorsal pancreas. Glucagon, on the other hand, is not expressed in the pancreas until stage 45. In the endocrine cell clusters we do not find glucagon-expressing cells surrounding insulin-expressing cells, either in the tadpole or in the mature frog pancreas.     

Influence of B-cell impairment on pancreatic acini in NOD mice and streptozotocin-induced diabetic rats

Exocrine pancreatic function insufficiency, even of short duration, has been reported in juvenile-onset insulin dependent diabetic patients. To evaluate the status of pancreatic acini under decreased B-cell function, tissue insulin, amylase, chymotrypsinogen and trypsinogen in the pancreas were measured in streptozotocin-induced diabetic rats and non-obese diabetic mice in various conditions. In streptozotocin diabetic rats, a dissociation of three enzyme contents was demonstrated in the condition with discontinuation of insulin injection, i.e., a marked decrease in amylase, a significant increase in chymotrypsinogen, but no significant change in trypsinogen. This dissociation was markedly improved in the insulin-treated condition. In non-obese diabetic mice, these enzyme contents were not significantly changed although severe insulitis together with the marked decrease in insulin content was observed. These data show that the cessation of B-cell function alone does not cause insufficiency of exocrine pancreas.