Pancreatic Enzyme Content Research Articles

Pancreatic islets isolation using different protocols with in situ flushing and intraductal collagenase injection.

Human islet transplantation seems to be a very promising clinical procedure for patients with type I diabetes mellitus. The aim of our study was to investigate the influence of in situ intravascular flushing with University of Wisconsin (UW) solution and intraductal collagenase injection at the time of pancreas procurement on the isolated islets and exocrine tissue injury. Our experiments indicated that in situ perfusion with the UW solution has a beneficial effect on pancreatic islets and intraductal distention results in an increase in the concentration of pancreatic enzymes released into the cold preservation solution during ischemic conditions. Cold ischemia reduced islet yield, but pancreas perfusion with the UW solution showed better ischemic tolerance of isolated islets during glucose static incubation. We conclude that intravascular pancreas flushing has a crucial effect on recovery and yield of pancreatic islets and protects against exocrine tissue injury.

Equine trypsin: purification and development of a radio-immunoassay.

Shock is accompanied by generalised splanchnic hypoperfusion, and splanchnic organs like the pancreas can be damaged, as shown in animal experimental models and in humans, by the presence of high plasma concentrations of trypsin and other pancreatic enzymes. In order to design a radioimmunoassay technique (RIA) for the measurement of equine trypsin-like immunoreactivity (TLI) in biological fluids, trypsin was purified (with purity > or = 96%) from the equine pancreas by extraction in an acid medium, ammonium sulfate precipitations, gel filtration chromatography and, after activation of trypsinogen into trypsin, affinity chromatography. Gel polyacrylamide electrophoresis showed a monomeric enzyme with a molecular weight of 27 kDa. The purified equine trypsin served for the immunisation of rabbits in order to obtain a specific antiserum, and the labelled antigen was prepared by iodination of equine trypsin with 125I. The RIA was based on the binding of the antigen to the antibody followed by the separation of the antigen-antibody complex by immunoprecipitation in the presence of sheep anti-rabbit gammaglobulins and the assay of the radioactivity in the precipitate. The RIA showed good sensitivity, specificity, precision, accuracy and reproducibility. The reference mean value of TLI in the plasma of healthy horses (n = 20) was 30.01+/-6.84 ng/mL (upper confidence limit 50.52 ng/mL; p < 0.01). Three horses with non strangulating intestinal obstruction without shock showed TLI values within normal limits whereas 5 of 7 horses with strangulation obstruction showed TLI levels above the upper confidence limit. Further studies using the RIA and the enzymatic assay should be performed in order to confirm the role of the pancreas in equine intestinal obstruction.

Influence of pancreatic enzyme content on experimental acute pancreatitis.

Some studies demonstrate the crucial role of proteases in the pathogenesis of acute pancreatitis (AP). Systemic release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) has been demonstrated in AP, yet the mechanism of activation remains unclear. Furthermore, it is not known if the amount of pancreatic enzyme in the pancreas determines the production of proinflammatory cytokines. To determine whether there is a link between the pancreatic enzyme content and the production of cytokines and consequently the systemic lesions observed in AP. Forty-seven animals were divided into three groups: group I had a high pancreatic enzyme level (with and without AP), group II had a low pancreatic enzyme level (cerulein infusion: 0.133 microg x kg(-1) x h(-1)) (with and without AP), and group III were the controls. AP was induced by injection of 5% sodium taurocholate into the pancreatic duct. To evaluate the pancreatic enzyme contents before AP, trypsinogen and amylase analysis was carried out on pancreatic tissue collected after the animals were killed. Two hours after induction of AP, concentrations of pancreatic enzymes and trypsinogen activation peptide (TAP) in serum, ascitic fluid, and pancreatic tissue were determined. The ascitic fluid was assayed for TNF-alpha and the serum was assayed for IL-6 with ELISA kits. Systemic lesions were sought on the basis of hepatic mitochondrial respiratory function measured polarographically. The administration of physiological doses of cerulein diminishes the pancreatic enzyme and TAP levels, the production of proinflammatory cytokines, and the liver mitochondrial dysfunction observed in AP, suggesting that the pancreatic enzyme content is an important factor in the severity of AP.

Effects of Octreotide Pretreatment in Experimental Acute Pancreatitis

Background: Severity of systemic lesions and mortality of experimental acute pancreatitis (AP) are reduced after pancreatic enzyme content reduction induced by cerulein administration. Octreotide has been used both prophylatically and therapeutically in AP. The possible effects of octreotide on pancreatic enzyme content and its influence on pulmonary lesions of experimental AP were assessed in this study. Methods: Wistar male rats were divided in two branches: Branch I – Animals divided into three groups: Group Sa (n = 10) intravenous saline infusion; Group Ce (n = 10) intravenous cerulein infusion, (0.133 µg/kg^–1·h^–1) and Group Oc (n = 10) SC octreotide (10 µg/kg^–1). Trypsin, elastase and amylase pancreatic contents as well as serum amylase were determined thereafter in all three groups; Branch II – Rats treated as in branch I, were submitted to sodium taurocholate AP (Groups Sa+AP, Ce+AP and Oc+AP). Two hours thereafter amylase and TAP assays were performed in serum, ascites and pancreatic tissue in eight animals of each group. Pulmonary histology was studied by morphometry 24 h after AP in the remaining animals. Results: Increased serum amylase and pancreatic enzyme contents were observed in octreotide-treated animals when compared to animals receiving saline or cerulein. After AP increases of serum and ascitic fluid amylase and of pancreatic TAP were observed in octreotide pre-treated animals when compared to saline and cerulein groups. Pulmonary interstitial and alveolar edema after AP was significantly increased in rats receiving octreotide as compared to the cerulein group. Conclusion: Octreotide administration acutely increases the enzymatic content of the pancreas and thus may have a potential deleterious influence in the evolution of AP.

Intestinal function and body growth of broiler chickens on diets based on maize dried at different temperatures and supplemented with a microbial enzyme.

A study was conducted to evaluate the effects of varying drying temperature (Fresh, 85, 95 or 105 degrees C) on the nutritive value of maize and response of broiler chickens to diets based on such grain, and supplemented with a microbial enzyme (Avizyme 1500). The chemical composition of the grain was affected by drying temperature. Starch and amylopectin contents were increased while there was a reduction in amylose content. These changes were expected to underlie the response of chicks to the diets. Total feed intake over 28 days was increased (P < 0.05) as a result of heat-treating the maize up to 95 degrees C. The final body weight of chicks on the diet based on fresh maize was improved (P < 0.05) by the microbial enzyme supplement (MES). There was no effect of the enzyme supplement on body weight when assessed at earlier ages. Over the entire feeding period, feed conversion efficiency (FCE) declined (P < 0.001) with increasing oven temperature, regardless of the supplementation with the microbial enzyme. Body weight was influenced (P < 0.05) by the microbial enzyme only when assessed over the entire trial period. The weight of visceral organs, protein content and activities of pancreatic and jejunal digestive enzymes were unaffected by grain heat treatment or MES. The ileal digestibility of calcium was reduced (P < 0.001) on diets based on fresh maize and maize that was oven-dried at 105 degrees C. Heat-treatment also improved (P < 0.05) the ileal digestibility of phosphorus in chicks on the diets without MES. There were no effects of grain heat treatment or MES on the ileal digestibility of energy, protein, Ca and amino acids. The results indicate some variations in grain quality as a result of heat treatment but the differences were not significant enough to stimulate major responses to the MES. Further studies should examine samples from commercial drying processes or samples obtained from a closer simulation of commercial conditions, to arrive at more practical conclusions.

Analysis of duodenal drainage fluid after cholecystokinin (CCK) stimulation in healthy volunteers.

Hormonal stimulatory agents are used to assess pancreatic function. Biologically derived secretin, the most widely used pancreatic secretagogue, is no longer available in the United States. Existing secretory tests using cholecystokinin alone are cumbersome, requiring a unique dual tube (gastric and duodenal) collection system and constant perfusion of a nonabsorbable marker to calculate enzyme output (in international units [IU]). A simpler, quantitative cholecystokinin stimulation test that measures enzyme concentrations (in international units per liter [IU/L]) instead of total output would obviate need for marker perfusion/collection. The aim of our experiment was to study the secretory patterns of pancreatic enzyme concentration in duodenal fluid after cholecystokinin stimulation in healthy volunteers. Healthy subjects had a Dreiling tube inserted endoscopically into the ligament of Treitz. Gastric and duodenal aspiration ports were connected to low intermittent suction. A 20-minute baseline was obtained to clear the gastric and duodenal lumina of residual fluid. Cholecystokinin was infused at a constant rate of 40 ng/kg per hour. Duodenal fluid was collected on ice for 80 minutes in four 20-minute aliquots. Aspirated fluid was analyzed for enzyme concentration with an automated chemistry analyzer in the hospital biochemistry laboratory. Nineteen healthy volunteers were studied. The mean volume (+/-SEM) of duodenal fluid collected was 85 +/- 4.4 mL (range, 48 to 118 mL). Fluid analysis revealed a significant rise in mean lipase concentration (+/-SEM) from a baseline of 595,680 +/- 11,930 IU/L to a peak of 1,778,847 +/- 171,204 IU/L (mean difference = 1,183,167 IU/L; 95% CI= 664,459 IU/L to 1,701,875 IU/L; < 0.001, Student test). Increases in amylase concentrations were markedly less pronounced and did not reach statistical significance. Mean peak lipase concentration occurred within 50 minutes of acinar cell stimulation. All patients tolerated tube placement, and there were no episodes of acute pancreatitis or abdominal pain. Pancreatic lipase concentrations in duodenal fluid increase nearly threefold after cholecystokinin stimulation in healthy volunteers. This magnitude of enzyme secretory response may be a marker of pancreatic function and could potentially lead to a more clinically useful and simpler pancreatic function test. This physiologic study serves as the basis for our further investigations of cholecystokinin-stimulated lipase concentrations as a new test in the assessment of pancreatic insufficiency.

Histoire naturelle du moignon pancréatique après duodénopancréatectomie céphalique (DPC)

Major complications following pancreaticoduodenectomy are thought to be chiefly associated with exocrine secretion of the pancreatic remnant which is not well known. This work aims to assess the exocrine secretion of the pancreatic remnant within the early post-operative period. Patients and methods: Seventy-five patients undergoing pancreaticoduodenectomy for presumed tumour were included in a prospective multicentre study. A tube was inserted in the pancreatic duct at the time of construction of the pancreatic anastomosis. Peripancreatic drainage was routinely used. Pancreatic juice and peripancreatic drainage fluid were collected and measured and pancreatic enzyme monitored. For 7 days patients received total parenteral nutrition and continuous infusion of randomly Somatostatin 14 (S-14) at a dose of 6 mg/24 h (days 1–6) and 3 mg/24 h (day 7) or matching placebo. Pancreatic fistula was defined as a daily drainage of more than 100 cc of amylase-rich fluid after day 3, persisting after day 12 or associated with symptoms or needing specific treatment. Results: Daily output of pancreatic juice was low during the first postoperative day and then increased gradually until day 5. A high enzyme concentration was observed in pancreatic juice on the first post-operative day. S-14 infusion resulted in a significant decrease of both pancreatic fistula rate and enzyme concentration in peripancreatic fluid. Conclusions: During the first postoperative days, the outflow of the exocrine secretion of the pancreatic remnant is low but contains a high enzyme concentration with significant leaks within the peripancreatic area. S-14 infusion results in a decrease of pancreatic juice leaks from the pancreatic remnant.

Role of CCK-A Receptor for Pancreatic Function in Mice: A Study in CCK-A Receptor Knockout Mice

The cholecystokinin (CCK) family of peptides and receptors is present throughout the brain and gastrointestinal tract. The CCK receptors can be pharmacologically subdivided into two subtypes: CCK-A and CCK-B. CCK-A receptor is enriched in the pancreas of mice. To determine pancreatic functions in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. To examine exocrine functions, amylase release from the dispersed acini in vitro was examined. In the in vivo study, the mixture of bile-pancreatic juice was collected, and amylase, bicarbonate, and bile acid outputs were determined after the administration of various stimulants. The cystic duct of the gallbladder and the pylorus were ligated to exclude the involvement of gallbladder contraction and gastric acid. Pancreatic enzyme content was measured, and histologic examinations by HE and lacZ staining were conducted. To examine endocrine functions, oral glucose tolerance test (2 g/kg) was determined. The body weight, pancreatic wet weight, and enzyme content in the pancreas were similar among the three genotypes. Amylase release in vivo and in vitro and bicarbonate secretion in vivo were not stimulated by CCK-8 in CCK-AR (-/-) mice, whereas the responses to other stimulants were substantial in (-/-) mice. Administration of secretin did not increase bicarbonate secretion regardless of genotype. A normal glucose tolerance was observed in (-/-) mice. Acinar cells, islets, and duct cells were stained by lacZ, and HE staining revealed no pathologic findings. The CCK-A receptor is important for pancreatic exocrine secretion, but not essential for maintaining glucose concentration and pancreatic growth in mice.

Pancreas after kidney transplantation.

After three decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for patients with insulin-dependent diabetes mellitus (IDDM) and advanced diabetic nephropathy with end-stage renal disease (ESRD) and for

Upper GI 23

Aims: Endoscopic sphincterotomy (ES) may result in bile duct malignancy in the long term: reflux of pancreatic enzymes into the bile duct may be contributory. To test this hypothesis, we assessed the degree of pancreatico-biliary reflux and associated biliary mucosal inflammation in patients with and without bile duct stones (CBDS) and after sphincterotomy. Methods: Bile was aspirated via cystic duct cannulation in 65 patients undergoing laparoscopic cholecystectomy ± ductal exploration. The quantity of chymotrypsin, lipase and amylase was measured in each sample. Comparisons were made between the following six patient groups: those with no current or previous CBDS (n = 14), patients without pancreatitis who had passed CBDS (n = 7), patients with pancreatitis with previous CBDS (n = 7), patients with current CBDS (n = 23), and patients who had undergone a previous ES, with (n = 7) and without current CBDS (n = 7). The degree of cystic duct inflammation was assessed for each patient by a histopathologist blinded to the clinical history. Results: Patients with no previous CBDS and those without pancreatitis with previous CBDS had negligible biliary concentrations of pancreatic enzymes and no cystic duct mucosal inflammation. Patients with current CBDS had mildly elevated amylase/lipase concentrations (4.1/2.2 activity units mL−1) and negligible cystic duct inflammation. In contrast, patients who had undergone ES (±CBDS) and those with recent pancreatitis had a moderate degree of cystic duct inflammation and higher amylase/lipase concentrations (24/16.2 activity units mL−1: P < 0.05 after ES; 136/61.8 activity units mL−1: P < 0.001 after pancreatitis). Chymotrypsin was only detectable in patients who had pancreatitis (6 activity units mL−1). Conclusions: High concentrations of pancreatic enzymes are only found in bile after a recent attack of acute pancreatitis and subsequent to ES: in both cases, there is associated mucosal inflammation. These changes may contribute to the late sequelae of ES.

Low enzyme content in the pancreas does not reduce the severity of acute pancreatitis induced by bile-pancreatic duct obstruction.

Enzyme load in pancreas has been considered a risk factor in the development of acute pancreatitis. In order to confirm this hypothesis our aim was to analyze the development and evolution of acute pancreatitis (AP) induced by bile-pancreatic duct obstruction (BPDO) after reducing the pancreatic enzyme content. L-364,718 - a potent CCK-receptor antagonist - was administered (0.1 mg/kg/day) for 7 days before inducing AP by BPDO. The course of AP was evaluated at different times from 1.5-48 h after BPDO. Amylase and trypsinogen contents and cytosolic calcium levels were measured by flow cytometry using specific antisera against pancreatic enzymes labelled with isothiocyanate of fluorescein and Fluo 3, respectively. The severity of the disease at the different stages was evaluated by measurements of amylase activity in ascites and plasma, percentage of pancreatic fluid and haematocrit. Electron microscopy study of the pancreas showed an increased number of zymogen granules spread through the acinar cells of control rats treated with L-364,718 for 7 days, however, total enzyme content in individual acinar cells was significantly (p < 0.01) diminished. AP significantly increased intracellular amylase and trypsinogen load from 3-12 h after BPDO, and prior L-364,718 treatment enhanced the blockade of enzyme secretion. As a result, acinar enzyme content was significantly increased from earlier stages (1.5 h after BPDO). In parallel, increased cytosolic calcium levels observed up to 24 h after BPDO appeared earlier in L-364,718-treated rats than in those not treated. The severity of AP seems to have been higher in rats previously treated with the CCK-receptor antagonist as indicated by the significantly higher pancreatic fluid and amylase activity in ascites and plasma observed at different times after BPDO. Our results indicate that there is no correlation between the severity of pancreatitis and the amount of enzymes accumulated in the pancreas before the disease is induced.

Cholecystokinin fails to promote pancreatic regeneration in diabetic rats following the induction of experimental pancreatitis

The aim of the present study was to investigate the spontaneous and cholecystokinin-octapeptide (CCK-8)-promoted laboratory changes and morphological alterations in rats with arginine (Arg)-induced pancreatitis in which diabetes had been induced with streptozotocin (STZ). Male Wistar rats were used in our experiments. Pancreatitis was induced by arginine, diabetes by STZ and regeneration was promoted by CCK-8. The serum amylase, glucose and insulin levels, the pancreatic contents of protein, DNA, amylase, trypsinogen and lipase, the pancreatic weight/body- weight ratio (pw/bw) and the plasma glucagon level were examined 1, 3, 7, 14 and 28 days after pancreatitis induction. Pancreatic tissue samples were examined by light microscopy and immunostaining on paraffin-embedded sections. The insulin and glucagon-containing cells were visualized by using monoclonal antibodies. The administration of low doses of CCK-8 accelerated the processes of regeneration following Arg-induced pancreatitis, but in rats that were also diabetic, pancreatic regeneration was not observed. The administration of low doses of CCK-8 seems to reduce the pancreatic β -cell number and function in diabetic rats. The pancreatic endocrine function was further deteriorated by simultaneous Arg-induced pancreatitis. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this study.

Continuous enteral feeding has an attenuating effect on the exocrine pancreas in rats.

Recent clinical observations suggest that continuous enteral feeding (CEF) may exert a beneficial effect in the management of inflammatory pancreatic diseases. Its effects on the exocrine pancreas, however, remain only partially investigated. To examine the effects of CEF on the exocrine pancreas in rats. Eight male Wistar rats were intrajejunally cannulated, and CEF was started on postoperative day 6. In 10 control animals, laparotomy was followed by intragastric feeding (GF) with the same nutriment (Osmolite, Abbott) from postoperative day 6. The daily discharge was 24 kcal in both groups. After 5 days of feeding, the pancreas was removed; its weight and its protein, DNA, trypsin, and lipase contents were determined; and the exocrine pancreas was also examined for structural changes. The results revealed no significant difference in body weight loss between the two groups of animals, whereas the pancreas weight/body weight ratio was lower (p < 0.01) in the CEF group. The pancreatic protein, DNA, and enzyme contents were decreased (p < 0.01) after CEF as compared with the values for the GF group. Histologic examinations demonstrated clear decreases in acinar size and in the zymogen content of the pancreas in the CEF animals. This study clearly indicates that CEF reduces the enzyme production of the pancreas.

Chronic Subcutaneous Octreotide Decreases Gastrointestinal Blood Loss in Blue Rubber–Bleb Nevus Syndrome

ABSTRACTBackgroundA patient affected by blue rubber–bleb nevus syndrome had chronic gastrointestinal bleeding requiring weekly blood transfusions. Despite multiple surgical and endoscopic procedures to treat the venous malformations, the patient continued to bleed primarily from lesions in the small bowel. Therefore, this patient was treated with octreotide, a somatostatin analog known to decrease splanchnic blood flow and that is used for acute and chronic gastrointestinal bleeding.MethodsOctreotide therapy, 5.7 μg/kg subcutaneously twice daily, was initiated, and the patient was followed up clinically. Complete blood counts, blood glucose concentration, pancreatic enzyme concentration, liver function tests, and growth hormone concentration were monitored during treatments.ResultsDuring the 4 weeks after initiation of octreotide therapy, hemoglobin concentration was maintained without the need for transfusions. Octreotide decreased the patient's monthly need for blood transfusion from 52 ± 7 mL · kg−1 · mo−1 of packed red blood cells to 23 ± 7 mL · kg−1 · mo−1. She had no detectable side effects or growth inhibition. Other medical interventions including ‐εaminocaproic acid, nadolol, and total parenteral nutrition with bowel rest were not as effective as octreotide alone.ConclusionOctreotide decreased the patient's need for blood transfusions. Possible mechanisms include altering blood flow to the gastrointestinal tract and direct effects on the venous malformations.

Influence of pancreatic enzyme content on the pathogenesis of acute pancreatitis

Influence of pancreatic enzyme content on the pathogenesis of acute pancreatitis

Influence of pancreatic enzyme content on the pathogenesis of acute pancreatitis

Influence of pancreatic enzyme content on the pathogenesis of acute pancreatitis

Influence of pancreatic enzyme content on pulmonary lesions of experimental acute pancreatitis

Background Pulmonary insufficiency is a frequent complication of acute pancreatitis (AP). Intravenous administration of cerulein in small doses decreases the pancreatic enzyme content and reduces the mortality rate of experimental AP. We studied the influence of pancreatic enzyme reduction on the pulmonary lesions of experimental AP. Methods Pulmonary oedema was evaluated by microscopic lung morphometry in rats 24 hours after the induction of sodium taurocholate (Na + Tachol) AP, with and without a previous intravenous injection of cerulein. Experimental groups were as follows: Group I: No cerulein infusion and AP induced by Na + Tachol at 2.5% (Group IA) and at 4% (Group IB); Group II: Previous cerulein infusion and AP induced by Na + Tachol at 2.5% (Group IIA) and at 4% (Group IIB); Group III: Cerulein infusion without AP. Results Reduction of pulmonary oedema was demonstrated in Group II when compared with Group I (p Conclusion Reduction of pancreatic enzyme content reduces the severity of pulmonary lesions in acute experimental pancreatitis.

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.

EFFECT OF [formula omitted] -AMINOCARNITINE, AN INHIBITOR OF MITOCHONDRIAL FATTY ACID OXIDATION, ON THE EXOCRINE PANCREAS AND LIVER IN FASTED RATS

Fasting induces pancreatic secretory lipase, possibly through an increased utilization of fatty acids and/or ketone bodies by the acinar cells. To test this hypothesis, the effects of l -aminocarnitine (ACA), an inhibitor of mitochondrial β-oxidation and ketone body formation, on the pancreatic enzyme composition were studied in rats. The characteristics and reversibility of the hepatic steatosis produced by ACA in fasted animals were also investigated. In fasted rats, ACA decreased the plasma levels of β-hydroxybutyrate, glucose and insulin, but increased that of glucagon. Fasting for 3 days increased the pancreatic lipase content by 80%. Administration of ACA (3, 10 or 30 mg kg−1daily) for 3 days to fasted rats led to dose-related decreases in pancreatic lipase content, the fasting-induced increase was prevented even by the lowest dose. Nevertheless, ACA in the fasted rats likewise decreased the pancreatic contents of protein, amylase and trypsinogen to varying degrees, suggesting a general defect of protein synthesis. The 3-day treatment with ACA during fasting led to dose-related, marked increases in hepatic weight and triglyceride content. Light and electron microscopy revealed lipid vesicles of varying sizes in the hepatocytes; the fat deposition was predominant in the periportal zones of the hepatic lobules. By means of electron microscopy, lipid vacuoles were observed in the centroacinar cells, but not in the acinar cells of the pancreas. In rats treated with 30 mg kg−1of ACA daily for 3 days while they were fasted, cessation of ACA treatment and refeeding with normal chow led to normalization of the pancreatic enzyme contents within 6 days, and gradual and complete disappearance of the hepatic steatosis within 24 days. Microscopy also demonstrated complete recovery in both the liver and the pancreas. The results indicate that pancreatic secretory lipase induction during the adaptive phase of starvation is dependent on an unhindered mitochondrial β-oxidation of fatty acids and ketogenesis. The dose-related degree of hepatic triglyceride accumulation which can be produced readily by administration of ACA during short-term starvation in the rat may serve as a new, convenient experimental model for studies of fatty liver. 2000 Academic Press@p$hr

Pancreatic Growth after Pancreatico-Biliary Diversion Does Not Increase the Capacity to Secrete Amylase

Background/Aim: Cholecystokinin (CCK) stimulates secretion and evokes a hyperplastic response in the rat pancreas. The aims of this study were to measure the effect of chronic hyperCCKemia induced by pancreatico-biliary diversion (PBD) on pancreatic enzyme concentrations, on amylase secretion by dispersed acinar cells, and on the CCK-stimulated secretion of pancreatic juice in PBD-operated rats. Material and Methods: Forty-five Sprague-Dawley male rats had either PBD or sham operation 4 weeks before sacrifice or additional experiments. In the first study, 25 rats (13 PBD and 12 sham-operated rats) were either freely fed or fasted overnight before sacrifice. The pancreas was dissected out, weighed and analyzed. In the second study, the rats (6 PBD and 7 sham-operated rats) were fasted overnight before pancreatic acini were prepared. Secretion of amylase during stimulation of acini with CCK-8S and carbachol was measured. In the third study (5 sham-operated and 4 PBD rats), the rats were fasted overnight before basal and CCK-stimulated secretion was measured in vivo. Results: PBD-operated rats showed a threefold increase in pancreatic wet weight with increased contents of DNA, protein and water. The concentration of pancreatic amylase was 7–12% of that found in control animals. The concentrations of trypsin and lipase were also lowered. Stimulation of dispersed pancreatic acini with CCK-8S or carbachol resulted in secretion of amylase to a similar extent in PBD and sham-operated rats. There was no difference in the secretion of pancreatic juice in response to CCK, but although the output of amylase from PBD-operated rats increased with CCK, it remained at a low level throughout the study period. Conclusion: PBD evoked hyperplastic changes in the rat pancreas and decreased the concentrations of amylase, trypsin and lipase. However, the capacity of acinar cells to secrete amylase remained intact. The stimulated pancreatic secretion was not changed in volume, but the output of amylase was low in PBD-operated rats. The findings are consistent with the idea that the enlargement of the pancreas following PBD does not improve the secretory capacity.