Effect of long-term administration of dietary fiber on the exocrine pancreas in the rat

Male Sprague-Dawley rats (50--70g) were fed a standard laboratory diet containing 6% dietary fiber substances (diet I), the same diet supplemented with 5% guar (diet II), 10% wheat bran (diet III), or 5% pectin of high (76%) methylic esterification (diet IV), or a fiber-free diet (diet V). After a 6-week feeding period, the body weight of the animals had increased to 300--350g. The common bile duct was then canulated and the exocrine pancreatic function tested under urethane anesthesia (1.5 g/kg body weight). The tested fiber substances had no effect on the basal pancreatic secretion of volume, bicarbonate, lipase, amylase or protein, or on the wet weight and histological appearance of the organ. However, the fiber substances influenced the pancreatic response to maximal exogenous stimulation with secretin (3.0 CU/100 g X hour) and cholecystokinin (0.6 IDU/100 g X hour) and the enzyme content of the gland significantly. Compared with diet V, diet I increased the DNA content of the pancreas and its secretion of bicarbonate and protein, and decreased the protein concentration in the gland. Diet II reduced the pancreatic content of trypsinogen and protein. Diet III decreased the protein content, but increased the bicarbonate secretion, which was also increased by diet IV. -- We conclude that fiber substances influence stimulated secretion and the enzyme content of the pancrease to a varying degree.     

Effect of caerulein on exocrine and endocrine pancreas in the rat.

The secretion of insulin, glucagon, pancreatic juice, and amylase in response to a 20-min iv infusion of synthetic caerulein were studied simultaneously in the anesthetized rat. Caerulein, a chemical analogue of cholecystokinin, was used in doses of 1-1000 ng/kg.min. The maximum stimulatory effect of caerulein on pancreatic juice volume and amylase output was obtained with doses of 10 ng/kg.min. With increasing doses, the effect decreased progressively. On the other hand, the release of insulin and glucagon was stimulated only by supramaximal doses of caerulein, which had little or no effect on pancreatic exocrine secretions. These results raised the question of whether, under physiological conditions, cholecystokinin regulates the secretory activity of the endocrine pancreas.     

Effect of chronic oral administration of the CCK receptor antagonist loxiglumide on exocrine and endocrine pancreas in normal rats

Summary Conclusion In normal adult rats, administration of a low dose of loxiglumide for 7 d had no significant effect on exocrine and endocrine pancreatic function, whereas a high dose of loxiglumide decreased pancreatic enzyme output without inducing insulin resistance and diabetes mellitus. Background There is a possibility that chronic administration of cholecystokinin receptor antagonists not only inhibits the growth of the pancreas but also alters exocrine and endocrine pancreatic function. Methods Loxiglumide at a dose of 50, 100, or 200 mg/kg body weight, or the same volume of saline, was given by an orogastric tube twice daily for 7 d (13 successive times). Biochemical and functional changes were determined on d 8 at 24 h after the last administration of loxiglumide and 18 h fasting. Pancreatic exocrine and endocrine function was simultaneously determined following an intravenous injection of a mixed solution of 0.5 g/kg body weight glucose plus 100 ng/kg body weight cerulein. Results Pancreatic weight and protein content were dose-dependently decreased by loxiglumide, whereas DNA content was decreased only by the highest dose of loxiglumide. Loxiglumide caused dose-dependent decreases in pancreatic fluid and protein output. Total pancreatic insulin content in rats treated with loxiglumide was not significantly different from that in the control rats. However, insulin concentration relative to DNA content was significantly increased in rats treated with 200 mg/kg body weight loxiglumide compared with that in other groups of rats. Glucose-stimulated insulin release was significantly low in rats treated with the highest dose of loxiglumide compared with that in other groups of rats, although there was no difference of serum glucose concentrations among these four groups of rats.     

Response of rat exocrine pancreas to chronic pulmonary ethanol intoxication

Rats were intoxicated over a 32-day period by continuous exposure to an ethanol-enriched atmosphere. Under these conditions, body weights increased up to day 26 and blood ethanol levels increased to approximately 2 g/liter. Pancreatic and hepatic histologies were normal. Amylase levels and total pancreatic protein decreased, while lipase levels rose. These changes appear to be independent of the caloric balance of the diet.     

Effect of cerulein hyperstimulation on the paracellular barrier of rat exocrine pancreas

Cerulein-induced pancreatitis causes a rapid increase in pancreatic enzyme levels in serum and decreases in pancreatic duct secretion and interstitial edema. One mechanism to explain these early events is disruption of the actin tight junction paracellular seal of acinar and intralobular pancreatic duct cells. To examine the paracellular barrier of the proximal exocrine pancreas, rats were hyperstimulated with 5.0 μg · kg⁻¹ · h⁻¹ of cerulein. Actin was visualized with rhodamine phalloidin and by electron microscopy and tight junctions were visualized with antibodies to the tight-junction protein ZO-1. Paracellular permeability was measured by movement of horseradish peroxidase from interstitium into duct or acinar lumens. In controls, linear actin and ZO-1 staining occurred along the apical membrane of intralobular duct cells and extended to the apical pole of acinar cells. Hyperstimulation caused progressive disruption of the linear staining of f-actin and ZO-1. Actin disruption in duct cells was confirmed by electron microscopy. Horseradish peroxidase entered intralobular ducts and acinar lumens of hyperstimulated animals more frequently than those of controls. The structure and function of the paracellular barrier of acinar and intralobular pancreatic duct cells are disrupted early during cerulein pancreatitis and may contribute to early clinical features.     

Effects of oxytetracycline on the rat exocrine pancreas

Summary Objectives. Given the appearance of pancreatitis attributed to tetracycline, as described in the literature, we have investigated its effect on the enzymatic content of pancreas and duodenal fluid and on pancreatic ultrastructure. We have evaluated possible differences between sexes and the relation of our findings with those described in the initial phases of acute pancreatitis, in the context of the acinar hypothesis. Methods. With 128 Wistar rats (63 male and 65 female), 3 groups were established: control (group I) experimental animals treated with oxytetracycline intramuscularly, 15 and 30 mg/kg/d (groups II and III, respectively). Before sacrifice, half of the rats in each group were stimulated with cholecystokinin. Blood, pancreatic tissue (for enzyme dosage and morphological study), and duodenal fluid were extracted following anesthesia. Results. The stimulated males of group III presented lower amylase levels in pancreatic tissue and duodenal fluid (P<0.003). Just the opposite occurred in female rats. A similar tendency was observed with other enzymes (lipase and trypsin). Zymogen granule counts, appearance of immature granules, and dilation of ergastoplasm were more frequent in the stimulated animals. Conclusions. Oxytetracycline seems to induce morphofunctional changes in rat pancreas, which differ according to sex. In the female, enzyme accumulation that could predispose intracellular activation seems to exist, as well as the ultrastructural findings described in initial phases of acute experimental pancreatitis. This agrees with the greater frequency of pancreatitis in women undergoing tetracycline treatment described in the literature. In contrast, for males the findings were more compatible with decrease of protein synthesis. This would make them less susceptible to crinophagy phenomena and, thus, to acute pancreatitis in the context of the acinar or lysosome hypothesis.     

Differentiation status of rat enterocytes after intestinal adaptation to jejunoileal bypass.

The differentiation status of epithelial cells in intestinal adaptation remains unclear. To determine whether enterocytes reach optimum maturity following adaptation after 85% shortening of the rat gut by jejunoileal bypass surgery, activities of two brush border enzymatic markers of differentiation, alkaline phosphatase and sucrase, were examined in subpopulations of epithelial cells isolated sequentially from the villus/crypt axis of normal (sham operated) and hyperplastic mucosa. In jejunal villi, adaptational hyperplasia was associated with an increase in total epithelial alkaline phosphatase, but not total sucrase, activity; alkaline phosphatase activity increased most obviously in cells at the 11-50% position (from the tip) on villi. In hyperplastic ileal villi, total alkaline phosphatase activity fell, although sucrase activity did not change significantly. Specific activity (per mg protein) of sucrase on jejunal villus epithelium was reduced by the adaptational changes to bypass; alkaline phosphatase specific activity remained unchanged. In the ileum, despite adaptational changes to bypass, there was no increase in the normally low specific activities of sucrase and alkaline phosphatase. Bypass surgery did not change the major site of expression of either enzyme on jejunal or ileal villi. In conclusion, enzymatic markers of functional differentiation are not all equally affected by adaptational hyperplasia. Hypertrophy of villi and increased cell proliferation seen in jejunum remaining exposed to luminal contents resulted in an increase in the alkaline phosphatase but not the sucrase content. This is not, therefore, the result of a simple immaturity of villus cells. Morphological adaptation in the ileum, however, is not accompanied by adaptation of brush border enzyme markers of differentiation, confirming a functional immaturity of these cells. Strategies for increasing the expression of these markers may have clinical value.     

Hyperplasia of the exocrine pancreas after small bowel resection in the rat.

The effect of a 90% small bowel resection on the exocrine pancreas was investigated over a three month period in adult Wistar rats. Control animals underwent a sham-resection consisting of a transection and reanastomosis of the small intestine. After jejunoileal resection, the wet weight of a gland increased significantly (52%) from the 15th day. The parallel increase in total protein, DNA and RNA content without any modification in the ratios of pancreatic weight, protein, and RNA to DNA suggests that there is cellular hyperplasia but not hypertrophy. Small intestinal resection decreased significantly the amount of amylase when expressed per unit pancreatic weight; it reduced slightly but not significantly that of chymotrypsin, while it did not modify the amount of lipase. However, the total amount of these enzymes in the pancreas remained unaltered when compared with controls. It is concluded that a massive resection of the small bowel induces cellular hyperplasia in the rat exocrine pancreas; this could compensate that reduced level of enzymes in acinar cells.     

Effect of long term alcohol feeding on the pancreas in rat

To elucidate the pathophysiological process of alcoholic pancreatitis, chronic alcohol intoxication was made in Wistar rats on balanced diet giving 20% ethanol freely for 60 weeks. The control rats received water. Histological picture of the pancreas, hormonal activity in the mucosa of upper digestive tract and the nature of pancreatic juice were examined in every 15th week. The results were as follows. 1) No histological changes were noted in the pancreas of control group. In the ethanol group, morphological abnormalities of the pancreas appeared after 30 weeks. Of the histological findings, the changes on the ductal system such as dilatation of pancreatic duct, plug formation in the ductal lumen and periductal fibrosis were significant. 2) The long term ethanol administration tended to decrease the amounts of gastrin, secretin and cholecystokinin contained in the gastrointestinal mucosa. 3) Regardless of the histological changes of the pancreas, almost no changes were noted in the bicarbonate and protein concentration during the experimental period of 60 weeks. From the above results, a mechanism obstructing pancreatic ductal system is considered to be important in the pancreatic lesions by alcohol rather than a mechanism of stimulating pancreatic exocrine secretion.     

Structural and functional effects of long-term alcohol administration on the dog exocrine pancreas submitted to two different diets

Our purpose was to study the influence of two different levels of dietary protein and fat on the action of chronic alcohol feeding on the exocrine pancreatic secretion and the pancreatic morphology of conscious dogs. Ten animals were provided with gastric and duodenal cannulas. Five of them (group H) received a high-protein (39% of calories), high-fat (34%) diet, and the five others (group L) a moderately low-protein (15%), low-fat (20%) diet. Animals were housed in closed kennels lightened with artificial light and did not have free access to sunlight. Five series of experiments were performed just before and 5 and 12 months after daily alcohol administration through the gastric cannula (2 g/kg/day). Volume, bicarbonate, and protein were measured under basal conditions after intragastric ethanol infusion (1.5 g/kg), under hormonal stimulation with 1 clinical unit (CU)/kg/h secretin or 1 CU/kg/h secretin plus 3 Crick Harper Rate (CHR) U/kg/h cholecystokinin (CCK), before and after intravenous ethanol 1.3 g/kg for 20 min, and after intragastric ethanol (1 g/kg) given with a meal. Group H was the most sensitive to the action of chronic alcohol feeding. At the end of 1 year of alcohol administration, volume and bicarbonate were not affected, but protein secretion was significantly increased in basal conditions and under secretin infusion, but not under CCK infusion or in response to a meal. The secretory pattern of these dogs was different from the response of dogs studied in previous experiments having the same diet but housed in an open kennel and having free access to outside and sunlight. In group L, protein was less affected, but volume and bicarbonate were significantly decreased 1 year under secretin stimulation. Histological damages were seen in the two groups characterized by a slight periacinar fibrosis and alterations of ductal cells. Acinar and ductal luminae were dilated and filled with protein plugs also present in pancreatic juice and able to stop the flow of juice. At the difference from human beings, these plugs were built up of all secretory protein but not of an insoluble fibrillar molecular form of pancreatic stone protein. This study confirms the role of chronic alcoholism on the formation of protein plugs and shows the influence of nutritional and environmental conditions.     

Effects of oxytetracycline on the rat exocrine pancreas.

OBJECTIVES: Given the appearance of pancreatitis attributed to tetracycline, as described in the literature, we have investigated its effect on the enzymatic content of pancreas and duodenal fluid and on pancreatic ultrastructure. We have evaluated possible differences between sexes and the relation of our findings with those described in the initial phases of acute pancreatitis, in the context of the acinar hypothesis. METHODS: With 128 Wistar rats (63 male and 65 female), 3 groups were established: control (group I) experimental animals treated with oxytetracycline intramuscularly, 15 and 30 mg/kg/d (groups II and III, respectively). Before sacrifice, half of the rats in each group were stimulated with cholecystokinin. Blood, pancreatic tissue (for enzyme dosage and morphological study), and duodenal fluid were extracted following anesthesia. RESULTS: The stimulated males of group III presented lower amylase levels in pancreatic tissue and duodenal fluid (P < 0.003). Just the opposite occurred in female rats. A similar tendency was observed with other enzymes (lipase and trypsin). Zymogen granule counts, appearance of immature granules, and dilation of ergastoplasm were more frequent in the stimulated animals. CONCLUSIONS: Oxytetracycline seems to induce morphofunctional changes in rat pancreas, which differ according to sex. In the female, enzyme accumulation that could predispose intracellular activation seems to exist, as well as the ultrastructural findings described in initial phases of acute experimental pancreatitis. This agrees with the greater frequency of pancreatitis in women undergoing tetracycline treatment described in the literature. In contrast, for males the findings were more compatible with decrease of protein synthesis. This would make them less susceptible to crinophagy phenomena and, thus, to acute pancreatitis in the context of the acinar or lysosome hypothesis.     

Effect of islet hormones on secretin-stimulated exocrine secretion in isolated perfused rat pancreas

To clarify the effect of islet hormones on pancreatic ductular cell function, we measured the exocrine secretion elicited by 10 pM secretin in the presence or absence of islet hormones using an isolated perfused rat pancreas model. Insulin significantly increased secretin-stimulated pancreatic juice secretion, but not protein secretion. The potentiating effect of insulin on pancreatic juice secretion was concentration-dependent, and the maximal effect was observed with 1 μM insulin. Ouabain, a specific Na⁺,K⁺-ATPase inhibitor, caused concentration-dependent inhibition of the potentiating effect of insulin without affecting secretin action. Glucagon (100 nM) significantly inhibited secretin-stimulated pancreatic juice secretion and also tended to inhibit protein secretion. A somatostatin analog, SMS 201-995 (10 nM) significantly inhibited both the pancreatic juice and protein secretion stimulated by secretin. The inhibitory effect of SMS 201-995 was concentration-dependent and was maximal at 1–10 nM. These results demonstrate that insulin potentiates the secretory response to secretin, at least partly by increasing Na⁺,K⁺-ATPase activity, whereas glucagon and somatostatin inhibit this response. Thus, pancreatic islet hormones regulate the secretory function of pancreatic ductular and centroacinar cells.     

Dual effects of hydrocortisone on exocrine rat pancreas

The acute and chronic effects of hydrocortisone on exocrine pancreatic function were examined in the isolated perfused rat pancreas. In the first part of this study, rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5, and 10 mg/kg body wt once daily for 7 days. Trypsin and lipase secretion in response to 100 pM cholecystokinin-octapeptide was significantly increased in rats with the two highest doses of hydrocortisone compared with controls, irrespective of whether calculated as the total amount of stimulated output of enzymes or related to the secretion of enzyme to the pancreas content. On the other hand, the secretory responsiveness of amylase to 100 pM cholecystokinin-octapeptide was maximal at the 5-mg dose, and decreased with higher doses. In the second part, 100 microM hydrocortisone was superimposed for 20 min on 100 pM cholecystokinin-octapeptide stimulation to examine the acute effects of hydrocortisone on exocrine pancreatic function in the isolated perfused rat pancreas. Addition of hydrocortisone caused a significant inhibition of the secretion of pancreatic juice and amylase. The present study has clearly demonstrated the dual effects of glucocorticoids on the pancreas: inhibition and potentiation. There is a possibility that chronic treatment with large doses of glucocorticoid may sensitize the acinar cells an induce hypersecretion of trypsin and lipase, whereas acute treatment inhibits secretory function of exocrine pancreas.     

BSP clearance as the most reliable criterion of hepatic dysfunction after jejunoileal bypass in the rat

In rats subjected to a 90% jejunoileal by-pass or in sham-operated controls, liver function was compared to plasma nutritional state and adaptation of the intestine in continuity over a period of 3 months. While the plasma levels of GOT, GPT, and esterases A and C as cholinesterase C did not differ in either group, the percentage of retention of BSP increased until 8 weeks, then returned progressively to control values 12 weeks after small-bowel bypass. In contrast, plasma nonesterified fatty acid levels decreased significantly until 6 weeks, then recovered control values over the following periods. Plasma total protein and albumin levels also diminished after jejunoileal bypass, the most marked decrease being at the 4th postoperative week. The increase in villus size following the intestinal bypass was considerably pronounced for the ileum between the 8th and the 12th week. These results suggest that BSP clearance is the most reliable criterion for hepatic dysfunction in the rat subjected to a jejunoileal bypass. In addition, the parallelism between the variations of BSP clearance, intestinal adaptation, and plasma nutritional state argue for the “nutritional” theory as the most probable explanation for the formation of hepatic lesions.     

Allyl alcohol-induced changes in the rat exocrine pancreas.

A histologic, histochemical and electron microscopic study was carried out on the rat exocrine pancreas 6-96 h after a single allyl alcohol intake. Histologically, acidophilia, necrosis and vacuolation of the pancreatic acinar cells were observed. Histochemically, a low but evident alcohol dehydrogenase activity could focally be demonstrated in the pancreatic acinar cell cytoplasm of the experimental and control rats. By electron microscopy, cytoplasmic lipid droplets, mitochondrial degeneration and necrosis were found in the acinar cells. Focal cytoplasmic degradation and vacuolation were seen in acinar, centroacinar and ductular cells of the pancreas. The findings are regarded as the consequence of the toxic action or acrolein that originates after allyl alcohol oxidation by alcohol dehydrogenase. Analogies between the liver and the pancreas in their response to acute allyl alcohol and chronic ethanol intake are discussed.