Soybean trypsin inhibitor and cerulein accelerate recovery of cerulein-induced pancreatitis in rats.

The role of exogenous and endogenous cholecystokinin has been studied in the process of pancreatic regeneration after acute pancreatitis. A mild form of pancreatitis was induced in rats by subcutaneous cerulein at 12 micrograms.kg-1, three times a day for 2 days. After 3 days of rest, the cerulein-treated rats were divided into four groups: rats with acute pancreatitis fed 20% casein, who received no treatment; rats fed 50% casein; rats fed 20% casein supplemented with 1% soybean trypsin inhibitor (SBTI); and rats fed 20% casein who received 1 microgram.kg-1 of subcutaneous cerulein, three times a day. Controls were fed 20% casein plus saline subcutaneously. Rats were killed after 5, 10, or 20 days of treatment. Pancreatitis resulted in significant decreases in pancreatic weight and contents of protein, amylase, chymotrypsin, RNA and DNA. During the regenerative process, 1 microgram.kg-1 of cerulein increased all parameters to control values within 5 days and induced pancreatic growth thereafter. SBTI restored the pancreas to normal after 10 days with cellular hypertrophy; the 50% casein diet gave a response similar to SBTI without hypertrophy. It can be concluded that cerulein and SBTI can accelerate pancreatic regeneration after an attack of acute pancreatitis.     

Glucagon inhibition of cerulein-induced hypertrophy of the exocrine pancreas

Glucagon is structurally related to secretin but inhibits the effects of secretin and cholecystokinin (CCK) on pancreatic secretion in vivo. Because secretin is a weak stimulant of pancreatic growth and potentiates the trophic effects of CCK, we hypothesized that glucagon might inhibit CCK-induced pancreatic growth. Four groups of 10 rats were injected with saline, glucagon (30 micrograms/kg, equimolar to a known trophic dose of secretin), cerulein (0.67 microgram/kg), or glucagon plus cerulein every 8 h for 5 days. The pancreas was excised, weighed, and assayed for total content of DNA, protein, amylase, chymotrypsinogen, and lipase. In control and glucagon-alone groups, the small intestine was also removed, weighed, and assayed for DNA, protein, and disaccharidase content. Glucagon alone decreased pancreatic DNA and increased lipase content. Compared with cerulein-treated animals, animals treated with glucagon and cerulein showed significant decreases in pancreatic weight and content of protein, amylase, and chymotrypsinogen. Although glucagon had significant effects on intestinal protein, maltase, and sucrase contents in certain segments, there was no clear pattern of response. The data suggest that glucagon may be an inhibitory regulator of pancreatic growth, acting to block the effects of CCK on pancreatic hypertrophy.     

Effect of alpha-glucosidase inhibitor on exocrine and endocrine pancreatic function in rats fed a high-carbohydrate diet consisting of sucrose or glucose

The effect of the alpha-glucosidase inhibitor acarbose on pancreatic exocrine and endocrine function was studied using the isolated perfused pancreata prepared from rats fed a normal (control diet) or an acarbose-containing sucrose- (ACS diet) or glucose-supplemented diet (ACG diet) for 10 days. Pancreatic amylase and insulin contents in rats fed the ACS diet were significantly decreased compared with those in rats with the control diet. Rats fed the ACG diet, however, had normal enzyme and hormone contents. Basal and cerulein-stimulated flow rates of pancreatic juice in rats with the ACS or ACG diet were similar to those in rats fed the control diet, suggesting that the pancreata from rats treated with acarbose have normal sensitivity and responsiveness to cerulein. On the other hand, cerulein-stimulated amylase output was significantly decreased in rats with the ACS diet, but was normal in rats with the ACG diet. Insulin secretion to both glucose and cerulein stimulation in rats fed the ACS diet was reduced by approximately 55% compared with the control rats. On the other hand, rats fed the ACG diet showed normal insulin secretion to glucose stimulation, although the insulin response to cerulein stimulation was reduced by 30%. These results suggest that the addition of acarbose to the sucrose-rich diet decreases the secretory responsiveness of amylase to cerulein stimulation and that of insulin to both glucose and cerulein stimulation. All these alterations, except the sensitivity of B cells to cerulein, can be normalized by replacing sucrose with glucose.     

Rapid adaptation of pancreatic enzyme secretion in the conscious rat. II. Effects of fasting and dietary modulation

The influence of fasting and dietary modulation on basal and stimulated pancreatic enzyme secretion was studied in conscious rats with cannulated pancreatic ducts. Two days' fasting decreased pancreatic secretion by about 30%. After stimulation of the secretion rate by acute derivation of pancreatic juice or by intravenous infusion of cerulein (0.2 micrograms/kg/h) no rapid change of enzyme composition was found. In further experiments, two groups of rats were fed with carbohydrate-rich and carbohydrate-poor diets, respectively. After pancreatic duct cannulation and a postsurgical recovery period, the diets were interchanged. An adaptation of pancreatic enzyme secretion to the new diet was observed in pancreatic juice. Stimulation of the secretion rate during the adaptation process by acute derivation of the juice or by intravenous infusion of either cerulein, secretin, carbachol or cerulein plus secretin did not further modify the composition of pancreatic proteins. 'Nonparallel' secretion of enzymes was never found when sufficient time for recovery from pancreatic duct surgery was allowed.     

Fasting prevents acute pancreatitis induced by cerulein in rats

We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 g/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitumthroughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivoand in vitro.Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.This work was supported in part by a grant from the Japanese Ministry of Health and Welfare and Grant-in-Aid for Scientific Research (C).     

Influence of aging upon pancreatic digestive enzymes

The effects of aging upon pancreatic digestive enzymes were studied in 27-and 3-month-old Fischer 344 rats. Mean pancreatic weight, protein and DNA concentration and content, and protein-DNA ratios did not differ in the two groups of animals. Pancreatic amylase concentration was reduced by 41% and lipase concentration was increased by 29% in the aging animals, whereas, trypsinogen concentrations did not differ. Young and aging rats were fed diets enriched with fat (72%) or sucrose (75%) for seven days to define whether the different enzyme contents were intrinsic to the aging process or adaptable. In young, but not in aging rats, lipase concentration increased 25% during high fat compared to high sucrose diet feeding. High starch diet feeding induced a 26% increase in amylase in young rats but not in the old. Trypsinogen concentration was unaffected by dietary manipulation. Jejunal enteropeptidase concentration was modestly reduced in the aging rat. Postprandial luminal concentrations of trypsin and amylase did not differ in the two groups. Thus, aging may induce modest changes in pancreatic digestive enzymes and in jejunal enteropeptidase which are unlikely to be physiologically important. However, the pancreas of aging rats does not adapt to changes in dietary intake as well as young rats.This work was sponsored in part by research grants from the NIH (AG 01625 and AG 04201-01).     

Influence of Dietary Protein Concentration and Quality on Response to Erythropoietin in the Polycythaemic Rat

S ummary . The effects were examined of dietary protein concentration and quality on the response of polycythaemic hypertransfused rats to 6 units of human urinary erythropoietin. Rats were either starved or fed one of 14 different diets. Four protein sources were used, having a quality gradient from 100 to about 24. Two proteins—casein and wheat gluten—were used at five different levels of concentration (5–25%) in the diet. The response of rats maintained on the standard diet (Purina rat chow, 23.4% protein/g) was taken as the normal standard. The response to erythropoietin was 25% of normal in starved rats and 35% of normal in rats put on a protein-free diet. When 10% protein in the diet was obtained by using high biological value proteins (egg yolk or casein) the response to erythropoietin was normal. When the same concentration was achieved by using low biological value proteins (wheat gluten or corn protein) the response to erythropoietin was undistinguishable from that of rats put on the protein-free diet. When rats were maintained on diets with different concentrations of casein (5–25%) a normal response was observed when protein concentration was 10% with no further changes at higher concentrations. When rats were fed diets with different wheat gluten concentrations (5–25%) the response to erythropoietin was subnormal. These data suggest that the ability of rats to respond normally to erythropoietin is dependent on a continuous dietary intake of proteins at levels which are dependent on their biological values.     

Enteroglucagon

The present study evaluated pancreatotrophic factors after massive small bowel resection. Specifically, we examined the role of enteroglucagon in compensatory pancreatic hyperplasia after proximal small bowel resection (PSBR) by using rats fed a fiber-free elemental diet or an elemental diet containing pectin. PSBR increased the net pancreatic weight as well as the protein, DNA, RNA, and amylase contents, and elevated plasma enteroglucagon levels. Pectin addition to the diet provoked a further increase in these parameters and significant positive correlations were found between the plasma enteroglucagon levels and the protein, DNA, and RNA contents of the pancreas. Plasma gastrin and CCK levels were not affected by the small bowel resection. These results indicate that enteroglucagon may exert a potent trophic effect on the pancreas after PSBR.     

Effect of a new cholecystokinin receptor antagonist loxiglumide on acute pancreatitis in two experimental animal models

We evaluated the effects of a new cholecystokinin (CCK) receptor antagonist, loxiglumide, in a model of mild pancreatitis induced by repeated injections of cerulein and in a severe necrotizing form of pancreatitis induced by retrograde ductal injection of sodium taurocholate (NaTc) in rats. A single subcutaneous injection or oral administration of 50 mg/kg of body weight of loxiglumide almost completely reduced the increases of serum amylase activity and pancreatic wet weight, and caused histologic improvements of the cerulein-induced acute pancreatitis when given 30 min before the first cerulein injection. Loxiglumide was also effective in reducing the elevated serum amylase activity, pancreatic wet weight, and histologic alterations even when administered after the induction of acute pancreatitis. However, loxiglumide offered no apparent beneficial effects when given 30 min before and 3 h after the induction of acute pancreatitis by NaTc as determined by changes in serum amylase activity, pancreatic wet weight, and histology. These results do not necessarily suggest that CCK is not important in the pathogenesis of pancreatitis, but do suggest that the sole blockade of peripheral CCK receptors is ineffective against NaTc-induced severe necrotizing pancreatitis.     

Endogenous cholecystokinin, the major factor responsible for dietary protein-induced pancreatic growth.

This study was undertaken to clarify the role of endogenous cholecystokinin (CCK) in induction of pancreatic growth stimulated by a high protein diet. Rats with i.v. jugular cannulae in place and kept in Bollman cages were adapted to 5% casein diet for 9 days and switched to 70% casein for 2 days. MK-329, a CCK receptor antagonist, and SMS 201-995, a somatostatin agonist, were continuously infused at 0.5 mg/kg/h and 5 micrograms/kg/h, respectively, starting at the onset of feeding 70% casein. The 5 and 70% casein control groups were infused with saline. Feeding 70% casein significantly stimulated pancreatic hyperplasia and tissue hypertrophy. MK-329 and SMS 201-995 totally prevented 70% casein-induced increases in pancreatic weight and total RNA and DNA contents. The results indicate that endogenous CCK is the major factor responsible for pancreatic growth induced by a high protein diet.     

Effect of CCK antagonists CR 1409 and CR 1505 on rat pancreatic exocrine secretion in vivo

The action of cholecystokinin (CCK) antagonists CR 1409 and CR 1505 on pancreatic exocrine secretion stimulated by exogenous and endogenous CCK was studied in vivo in anesthetized rats, and compared with proglumide. Intravenous administration of CR 1409 and CR 1505 in graded doses between 0.04 and 25 mg/kg/h resulted in a dose-dependent inhibition in pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 microgram/kg/h. CR 1409 is 1,000 times and CR 1505 is 267 times more potent than proglumide, based on the ED50 (effective dose for half-maximal inhibition) for CCK-8-stimulated amylase secretion. Intraduodenal administration of casein in a dose of 400 mg/h caused significant increases in plasma CCK concentration and pancreatic secretion of juice volume and outputs of amylase and trypsin. Both CR 1409 and CR 1505 in a dose of 5 mg/kg/h suppressed the increases in pancreatic juice volume and both amylase and trypsin outputs induced by casein given intraduodenally. These results indicate that CCK antagonists including CR 1409, CR 1505, and proglumide inhibit pancreatic exocrine secretion stimulated by not only exogenous, but also endogenous CCK in rats.     

Dietary effects on pancreatic exocrine function. Experiments on the isolated perfused rat pancreas

Studies of the response of the isolated perfused rat pancreas to three doses of secretin (5.0, 10.0, 18.75 U/h) and CCK (0.6, 1.5, 2.4 U/h) show that a 35-day administration of a carbohydrate-rich (60% carbohydrate, 3% fat, 20% protein) or fat-rich (34% fat, 11.3% carbohydrate, 29.8% protein) diet increases the sensitivity of the gland to these hormones compared to a standard diet (50.5% carbohydrate, 4% fat, 19% protein). The maximal secretory flow on stimulation by secretin and on a combined stimulation by secretin (2.5 U/h) plus CCK (1.8 U/h) is significantly (p less than 0.05 and p less than 0.01, respectively) lower in both experimental diets than in controls, whereas the maximal protein and enzyme secretion is diminished only in the secretin plus CCK-stimulated pancreas of rats fed a fat-rich diet. A carbohydrate-rich diet results in a relative increase in amylase secretion and decrease in lipase and chymotrypsinogen output. Compared to controls, the fat-rich diet leads to a stronger secretion of lipase and chymotrypsinogen and to a reduced amylase secretion. This adaptation of the exocrine pancreatic function is rather due to changes in the organ itself than to an altered hormonal stimulation.     

Cholecystokinin: a factor responsible for the enteral feedback control of pancreatic hypertrophyphy

Chronic diversion of pancreatic and biliary secretions away from the proximal small intestine results in pancreatic hypertrophy in adult rats. Serum levels of cholecystokinin (CCK) were measured in age-matched control and surgically diverted rats at various times after operation by a radioimmunoassay method that was specific for the sulfated form of CCK. The concentration of CCK was markedly increased in bypassed rats as compared with controls. The increases in circulating CCK in bypassed rats was substantiated by a bioassay method that measured physiologically active CCK. The degree of pancreatic hypertrophy and the increase in CCK levels both progressed with time up to 23 days after surgery. Linear regression analysis showed an apparent direct correlation between pancreatic weights and serum CCK levels (r = 0.99). Feeding bypassed rats with diets containing various pancreatic and biliary supplements did not abolish the hyperplastic response of their pancreata. However, feeding with diets supplemented with bile partially suppressed the increase in serum CCK levels, while a diet containing Cotazyme and bile completely suppressed this increase. The discrepancy between serum CCK levels and the degree of pancreatic hypertrophy in the supplemented bypassed rats was further demonstrated by the lack of correlation using linear regression analysis (r = 0.33). The observed pancreatic hypertrophy in the absence of high serum levels of CCK in the bypassed rats fed bile and Cotazyme supplements suggests that serum hypertrophic factors other than CCK may also be involved in the enteral feedback regulation of pancreatic growth.     

Reversal by glucose of pancreatic amylase insufficiency in chronic alcoholic rats

Carbohydrate consumption regulates pancreatic amylase synthesis in rats. The Lieber-DeCarli 36% alcohol diet employed in chronic alcohol studies and the isocaloric control diet contain 11 and 47% of total calories from carbohydrates, respectively. Young rats fed ad libitum the 36% ethanol diet for 2 weeks obtained 1.2 g/day of carbohydrate, whereas those pair-fed with control diet received 5.8 g/day. Rats fed the 36% ethanol diet and given an intramuscular injection of a solution of 1.5 g of glucose daily for 2 weeks received twofold greater amounts of carbohydrate than saline-injected controls (2.7 versus 1.2 g). These changes in carbohydrate intake produced proportionate changes in pancreatic amylase levels. The secretory responses to cholecystokinin-octapeptide (CCK8) of acini from control and glucose-injected rats were significantly higher compared with those in the saline-injected or noninjected alcohol groups. The blood alcohol levels in glucose-injected rats were markedly reduced compared with other alcohol groups (71.7 versus 274.9 mg/dl) despite similar amounts of ethanol ingestion daily (2.4 g) in the three groups. In vitro experiments with acini from rats fed a nutritionally optimal diet revealed that high pharmacologic concentrations of ethanol, while inducing basal secretion, inhibited CCK8-stimulated amylase secretion. These results indicate that: (a) the amount of alcohol consumption does not correlate with either the levels of blood alcohol or of pancreatic amylase; (b) the carbohydrate availability in rats regulates pancreatic amylase levels despite significant levels of alcohol in blood; (c) blood alcohol levels observed in vivo may not affect synthetic and secretory processes of amylase in pancreatic acini.     

Fish protein stimulated the fibrinolysis in rats

OBJECTIVE: We hypothesized that fish protein affects blood coagulation and/or fibrinolysis, and compared the activity and amounts of factors involved in blood coagulation and fibrinolysis in rats fed the fish protein, which was treated to remove water-soluble and ethanol-soluble elements, from sardine (sardine protein). METHODS: In the first experiment, rats were fed for 21 days an AIN-93G-based control diet, and diets in which the casein of the control diet was exchanged for sardine protein at 5, 10 and 20% levels. In the second experiment, rats were fed an AIN-93G control diet and diets containing 5% fish oil, 10% sardine protein or both (5% fish oil + 10% sardine protein) for 21 days. At the end of the experiments, blood coagulation time, hemostatic parameters and fibrinolysis parameters were measured. RESULTS: The activated partial thromboplastin time (APTT), which is an assay for blood coagulation time in the intrinsic blood coagulation pathway, of rats fed the 20% sardine protein diet was significantly prolonged compared to that of rats fed the control diet. The prolonged APTT by dietary sardine protein was due to a significant decrease of the activities of plasma blood coagulation factors VIII, IX, XI and XII. On the other hand, dietary sardine protein significantly increased the activity of tissue-type plasminogen activator, and the amount of plasma plasmin-alpha(2)-plasmin inhibitor complex, which are markers of activated plasmin. Moreover, we observed that the 20% sardine protein diet increased the amount of plasma D-dimer, which is a degraded product of the fibrin polymer by plasmin. In the second experiment, the APTT and PT of rats fed the F diet were prolonged compared to those of rats fed the control diet, however the concentration and amount of fibrinolytic parameters in the plasma were almost the same as those of rats fed the control diet. In contrast, the F+S diet not only prolonged APTT and PT, but also increased the concentration and amount of fibrinolytic parameters in plasma. CONCLUSIONS: We consider that the beneficial effects to health and amelioration of cardiovascular and cerebrovascular diseases by fish consumption are caused by a combination of the suppressing effect on blood coagulation of n-3 polyunsaturated fatty acids and the promoting effect on fibrinolysis of fish protein.     

Effect of parental malnutrition on enzyme content of rat pancreas

The aim of this study was to assess in rat pups the influence of protein diets ingested by their mothers during gestation and lactation on the enzyme content of the pancreas of the offspring. Rat pups born of either well-nourished mothers or of mothers fed a diet moderately restricted in protein (9% casein w/w) were studied. After weaning, the pups were fed on one of three diets: a well-balanced diet, a 5% casein diet (protein restricted), or a well-balanced diet of a similar caloric value as the protein-restricted diet (pair-fed rat pups). The pups were sacrificed after intervals of one to 25 weeks after weaning. The results showed that the enzyme content of the pancreas increased progressively with time in pups born of malnourished mothers, particularly in pups fed the protein-restricted diet. This suggests prolonged maturation of the pancreas. Pups fed the 5% casein diet had a decreased amylase content per milligram of DNA but not of other enzymes. Malnutrition in the mother inceased the ratio of enzymes to DNA and the total pancreatic enzyme content at different times after weaning, indicating that maternal malnutrition had a prolonged effect on the pancreatic enzyme content of the pups' pancreas. This mechanism could play a role in the pathogenesis of tropical chronic calcific pancreatitis in man and explain some of the geographic differences in the incidence of the disease.     

Effect of feeding maize/legume mixtures on biochemical indices in rats

Protein-energy malnutrition is one of the major public health problems in developing countries of the world due to prevailing socio-economic problems. This study aimed to observe the effect of formulated complementary blends on biochemical parameters of rats. Extruded complementary blends from maize fortified with cowpea or soybean at a level of 35% and 25% respectively were fed to 4 groups of rats for 28 days. Similarly, 3 other groups of rats were placed on casein, non-protein or rat pellet diet. Biochemical analysis was done on blood samples of the rats. Results from previous studies show the protein content of the formulated diets to range from 15.75% in UMC to 17.24% in MMS. Significantly (p < 0.05) lower WBC, Hb, MCHC, total protein, albumin and globulin values were recorded for the rats fed a non-protein diet (NP). The serum AST level was 75.5, 71.2, 63.2, 51.0, 60.5 and 55.7, respectively, for rats on casein, rat pellet, MMS, UMS, MMC and UMC (list of abbreviations is shown in the appendix) diets. Alkaline phosphatase was significantly (p < 0.05) higher in soybean-based diets while cholesterol was lowest in rats fed the non-protein diet (NP). The value obtained for serum electrolyte concentration in the rats fed NP compared well with rats on other diets but, however, had a significantly (p < 0.05) higher serum sodium value. These results confirm that the experimental diets supported growth, as shown in a previous study, and had no harmful consequence.     

Exogenous administration of estradiol and cholecystokinin alters exocrine pancreatic function in rats

Summary This study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.     

Casein-induced hypercholesterolaemia in rabbits is calcium-dependent

Young male rabbits were fed semi-purified diets containing either casein or soy protein, both at a normal (0.84%, w/w) and a high (1.44%, w/w) level of dietary calcium. At the normal calcium level, casein, as compared with soy protein, increased the concentration in serum of total and free cholesterol and the ratio of free cholesterol to phospholipid. Also, casein increased the intestinal phosphate absorption and decreased the faecal fat excretion. The hypercholesterolaemic response of the rabbits on the casein diet was significantly correlated with both phosphate absorption (r = +0.744) and fat excretion (r = -0.701). The increased amount of dietary calcium inhibited the casein-specific effects on both the intestinal and the serum lipid parameters. In contrast, calcium did not change these parameters in rabbits fed the soy protein diet. These results support the hypothesis that the degree of phosphorylation of casein is involved in the mechanism of the casein-induced hypercholesterolaemia by means of its effect on the enterohepatic cycle of bile acids.     

Manifestations of experimental acute pancreatitis in young and old rats

Two kinds of experimental pancreatitis were induced in young (4-6 month) and old (25-27 month) female Wistar rats: acute edematous pancreatitis was induced by intraperitoneal administration of a high dose of cerulein (40 micro/kg x 2) and acute hemorrhagic pancreatitis was intraductal injection of 1% deoxycholic acid. After these treatments, the plasma amylase concentration and pancreatic wet weight were determined and the pancreas was examined histologically. In the groups with cerulein induced pancreatitis one of eight old rats died, whereas all five young rats survived. There was no specific finding macroscopically in the liver, kidney, lung or heart of old rats at autopsy after cerulein injection. The plasma amylase concentration and the pancreatic wet weight were significantly increased by administration of cerulein or deoxycholic acid in both young and old rats. There was no significant difference in the plasma amylase concentrations in young and old rats after the induction of acute pancreatitis. The increase in pancreatic wet weight was less in old rats than in young ones after deoxycholic acid treatment, but similar in the two groups after cerulein injection. The extents of histological changes were also similar in young and old rats. Thus, no evidence that aging increases susceptibility to pancreatitis was obtained.