Endocrine pancreatic secretion in patients after acute pancreatitis

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.     

Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis

Pancreatic enzyme secretion is inhibited during acute pancreatitis, resulting in an increase in acinar zymogen content. Since the premature activation of zymogens has been assigned a central role in the pathogenesis of acute pancreatitis, minimizing the amount of stored zymogens might lead to less severe acute pancreatitis. Inhibition of enzyme synthesis or stimulation of enzyme secretion would result in reduction of zymogen stores. Opiates have a varying effect on pancreatic secretion, depending on the dosage, site of administration, and presence of pancreatic stimulants. The effect of opiates and acute pancreatitis on individual pancreatic enzyme synthesis is unknown. The following study was undertaken in order to examine the effects of an opiate on pancreatic enzyme secretion and synthesis during experimental acute pancreatitis. Four groups of rats were studied. Group I received cerulein (25 µg/kg); group II received an opiate, buprenorphine (BPN, 0.5 mg/kg); and group III received cerulein and BPN. Drugs were dissolved in gelatin/saline and injected subcutaneously. A control group (group IV) received only gelatin/saline. Rats were sacrificed 4 hr after injection, and pancreatic mass was measured. Pancreatic acini were prepared and assayed for amylase and DNA content. Amylase, trypsinogen, chymotrypsinogen and lipase synthesis, and amylase secretion were measured for 2 hr. Results showed that, compared to controls, acini of rats with AP had increased amylase content, a finding consistent with decreasedin vivo amylase secretion. Total protein and individual enzyme synthesis rates were significantly lower in the acini of the rats with AP than in those of the controls. Negative feedback inhibition of enzyme synthesis due to the increased stores of intracellular enzymes may account for these findings. BPN reduced pancreatic edema in rats with acute pancreatitis (AP). Acinar amylase content of rats with AP treated with BPN was significantly lower than in acini of rats with AP. As amylase secretion was lower in the AP + BPN rats, the reduced acinar amylase content was probably solely due to the reduction in enzyme synthesis observed in the AP + BPN rats. The results suggest that BPN may have a moderating effect on the development of AP.This study was supported by a research grant from the South African Medical Research Council.     

Exocrine pancreatic enzyme and calcium secretion in health and pancreatitis.

Calcium, enzyme, and total protein secretion were measured in secretin stimulated pancreatic juice in health, "early" chronic pancreatitis, and in chronic calcific pancreatitis. Increased concentrations of trypsin, total protein, and calcium, and increased outputs of calcium and protein were shown to be present in the "early" stages of the disease, indicating that an environment conducive to the formation of protein plugs and possibly later calcification already exists.     

Free proteolytic enzymes in pancreatic juice of patients with acute pancreatitis

Pancreatic juice from four patients with acute pancreatitis was collected at 4° C from uncomplicated fistulae or by catheterization of the pancreatic duct. The concentration of free trypsin, chymotrypsin, and elastase, as well as the corresponding zymogens in the specimens, was estimated. With the exception of the juice from one patient with a fistula, who secreted zymogens and free chymotrypsin only during the first two postoperative days, all specimens contained free enzymes exclusively, including those specimens obtained by catheter during the period of observation. The apparent lack of pancreatic trypsin inhibitor in the secretions of our patients, and earlier reports of low levels or absence of this inhibitor after abdominal operations, may reflect a prerequisite in the development of acute pancreatitis. In this scheme, the trigger mechanism in the premature activation of pancreatic zymogens may be provided by autoactivation of trypsinogen or its activation by enzymes of the blood-clotting or fibrinolytic systems. Some evidence in support of this hypothesis is presented.     

Endocrine pancreatic function in patients after acute pancreatitis

BACKGROUND/AIMS: The incidence of carbohydrate tolerance disorders in patients after acute pancreatitis has not been clearly established yet. The aim of the study was to estimate the frequency of endocrine pancreatic function impairment in patients after acute pancreatitis and its correlation with acute pancreatitis etiology and clinical course. METHODOLOGY: 82 patients (27 women and 55 men), aged between 28-65 (mean: 47 +/- 8.3), 1-7 (mean: 4.7 +/- 3.6) years after acute pancreatitis were evaluated. Control group consisted of 15 healthy volunteers. Oral glucose tolerance test with RIA insulin level was performed in all examined patients. Patients with any sign of chronic pancreatitis, based on clinical, functional (stool chymotrypsin test) and imaging (US and CT) findings, were excluded from the study. RESULTS: Impaired glucose tolerance was found in 4 patients (4.9%) and overt diabetes in 13 patients (15.8%) recovered from acute pancreatitis, which was not significantly different from those values in the local general population. Mean insulin values fasting and 30, 60 and 90 min after administration of 75 g glucose were significantly lower in patients after acute pancreatitis than in controls (p < 0.001). Endocrine pancreatic function impairment was found significantly more often in patients after severe acute pancreatitis clinical course (p < 0.0001), than in patients after mild pancreatitis. The frequency of impaired glucose tolerance and diabetes after acute alcoholic pancreatitis was 13 (36%), which was significantly higher (p < 0.05), than in cases of gallstone etiology (14%) and other causes (0%). CONCLUSIONS: Pancreatic endocrine function impairment following acute pancreatitis is associated with the decreased plasma insulin levels fasting and after glucose stimulus. Overall, the incidence of diabetes mellitus in patients after acute pancreatitis is similar to the reported values for the general population in this area. Alcoholic pancreatitis is more often complicated with impaired glucose tolerance and diabetes mellitus as regards to other causes of pancreatitis. Endocrine pancreatic function impairment is significantly more common after severe than after mild acute pancreatitis.     

Pancreatic polypeptide secretion in patients with chronic pancreatitis and after pancreatic surgery.

AIM: We investigated polypeptide (PP) secretion under basal conditions, in response to bombesin infusion and to meal ingestion in patients with chronic pancreatitis (CP) and patients after different types of pancreatic surgery. METHODS: Included were patients with CP without (n = 20) and with (n = 30) exocrine pancreatic insufficiency, patients after duodenum preserving resection of the head of the pancreas (DPRHP; n = 20), after Whipple's procedure (n = 19), following distal pancreatectomy (DP; n = 12), and healthy controls (n = 36). RESULTS: In CP patients basal and bombesin stimulated PP levels were significantly (p<0.01) reduced compared to controls only when exocrine insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01-0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma PP peak increments after bombesin and meal ingestion correlated significantly with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic pancreatitis. In patients after pancreatic surgery that included pancreatic head resection (DPRHP or Whipple operation) basal and stimulated PP secretion were significantly (p<0.01-0.05) reduced. CONCLUSION: Basal and meal or bombesin-stimulated PP levels are significantly reduced in patients with CP only when exocrine insufficiency is present. Determination of plasma PP levels has low sensitivity and is not useful in detecting chronic pancreatitis without exocrine insufficiency. In patients after pancreatic surgery, PP secretion is dependent on the type of operation (head vs tail resection).     

Effects of cocaine on rat pancreatic enzyme secretion and protein synthesis

The effects of cocaine on amylase secretion and total protein synthesis were studied by use ofin vitro rat pancreatic tissue.In vitro, cocaine (2 or 10 mM) did not modify basal release of amylase; at a concentration of 2 mM, it reduced the secretory response to pancreozymin by 32% and that to urecholine by 68%. Incorporation of amino acids into total proteins was decreased by 15% by cocaine 2 mM and by 49.5% at 10 mM. Administeredin vivo at a dose of 15 mg/kg intraperitoneally, cocaine was associated with decreases in protein synthesis 30, 90, and 180 min after its injection. These results indicate that cocaine can affect basic functions of the exocrine pancreas and reduce its response to secretagogues.Supported by the Medical Research Council of Canada: Non-Medical Use of Drugs Program.     

Measurement of pancreatic enzyme synthesis in humans. Problems in patients with calcific pancreatitis

Earlier studies have suggested that the rate of incorporation of labeled amino acids into duodenal juice proteins during pancreatic stimulation may be used to calculate pancreatic enzyme synthesis and function. In the present study, a pulse/4 h continuous intravenous infusion of 14C labeled leucine was used to compare synthesis rates in 6 patients with chronic calcific pancreatis(CP) to 4 controls. Analysis of duodenal juice protein demonstrated a delay of approximately 1 h in the appearance of labeled proteins, followed by a linear increase in specific activity, allowing calculation of synthesis that varied between 2.6-2.8 h in controls and 6-48 h in CP. The protein in controls was representative of enzyme protein, but that of CP was not, since it was heavily contaminated with albumin (up to 50%). The results indicate that enzyme secreted during the first hour of stimulation is derived from pancreatic stores and that the synthesis rate of enzymes secreted thereafter is approximately 2.7 h in normal humans. The method was, however, unable to determine rates in patients with CP owing to heavy contamination of enzymes with exudative proteins.     

Action of secretin on pancreatic enzyme secretion in man. Studies on pure pancreatic juice

The action of pure, natural secretin on the pancreatic secretion of enzymes was investigated in six patients with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Secretin infused for five successive 50 minute periods at increasing doses of 0.03, 0.1, 0.3, 0.9 and 2.7 clinical units (CU)/kg/h, produce a dose dependent increase in protein and lipase output. A weak but significant (p less than 0.02) increase of enzyme output above the fasting level was already observed with the lowest dose. The maximal output of protein and lipase, observed with the highest dose of secretin infused, corresponded to about 50% of that induced by maximal doses of cerulein (100 ng/kg/h) plus secretin (1 CU/kg/h). As far as bicarbonate is concerned, the lowest dose of secretin (0.03 CU/kg/h) significantly (p less than 0.001) stimulated bicarbonate output. The dose of 0.9 CU/kg/h of secretin evoked a bicarbonate output of 526 +/- 49 micromol/min; trebling the dose of secretin did not significantly increase the output of bicarbonate above this value. Increasing doses of secretin induced a dose related increase in calcium output. There was a close parallel between calcium and protein outputs, suggesting that the increase in calcium output reflected primarily an increase in the enzyme-associated fraction of pancreatic juice calcium. It is concluded that secretin stimulates pancreatic enzyme secretion in man probably by a direct action on the acinar cells.     

Duodenal total and ionised calcium secretion in normal subjects, chronic alcoholics, and patients with various stages of chronic alcoholic pancreatitis.

Previous studies have shown increased secretion of total calcium in the duodenal juice of patients with chronic alcoholic pancreatitis compared with healthy subjects. In order to get more detailed information on calcium secretion and pancreatic stone formation in chronic alcoholic pancreatitis, ionised and total calcium concentrations were determined in the duodenal juice of normal subjects, chronic alcoholics, and patients with various stages of chronic alcoholic pancreatitis. Total calcium secretion was in agreement with previously published data. Chronic alcoholics presented a significant increase of ionised calcium. In the course of pancreatitis all calcium fractions increased progressively revealing highest concentrations in patients with severe exocrine insufficiency. In non-calcified and calcified pancreatitis all calcium fractions were identical. It is suggested that the increase of ionised calcium originates from serum ionised calcium passing by diffusion into the damaged pancreatic duct system.     

Cholecystokinin secretion in patients with chronic pancreatitis and after different types of pancreatic surgery.

Cholecystokinin (CCK) secretion may be affected in patients with chronic pancreatitis (CP), but little is known on the effect of pancreatic surgery on CCK secretion. We measured CCK secretion (radioimmunoassay, RIA) in response to bombesin infusion (100 ng/kg/20 min) for 120 min to test CCK secretory capacity, to ingestion of a liquid diet (400 kcal) for 120 min, and in response to a solid fat-rich meal (500 kcal) for 120 min. These studies were performed in 45 patients with CP (25 with exocrine insufficiency), 15 patients after duodenum-preserving pancreatic head resection (DPRHP), 18 patients after the Whipple operation, 12 patients after distal pancreatectomy (DP), and 35 control subjects. In CP patients, the CCK secretory capacity was preserved, but the postprandial CCK response was reduced, depending on meal composition and the presence of exocrine insufficiency. In patients after Whipple's operation, CCK secretory capacity and postprandial CCK secretion were significantly (p < 0.05) reduced. In patients after DPRHP, CCK secretory capacity was not affected, but the postprandial CCK response was significantly (p < 0.05) reduced, depending on meal composition and the presence of exocrine insufficiency. In patients after DPRHP, fasting plasma CCK levels were significantly (p < 0.01) increased, pointing to the absence of feedback inhibition on CCK secretion by intraluminal enzymes. After DP, the CCK secretory capacity was not affected. In conclusion: alterations in CCK secretion are observed in patients with chronic pancreatitis and after pancreatic surgery. These alterations are related not only to the disease process (exocrine insufficiency) but also to the type of surgery and type of stimulus.     

Nonparallel secretion of antibacterial activity and protein in porcine pancreatic juice

The antimicrobial activity of exocrine pancreatic juice is an important component of gastrointestinal tract innate defenses, yet little is known about whether secretion is regulated in parallel with digestive enzymes. In this study, we used 8 pigs with pancreatic catheters to quantify antibacterial activity and measure protein content (indicator of enzyme secretion) of pancreatic juice collected hourly from 0700 to 1900, with the animals adapted to being fed at 0800 and 1600. Antibacterial activity in the samples of pancreatic juice was quantified by comparing the growth inhibition of Staphylococcus aureus subsp. aureus strain ATCC 6538P relative to a known concentration of gentamicin. Antibacterial activity (U/mL and /min) was highest in samples collected 1 hour prior to feeding (equivalent to 0.6 microgram gentamicin/mL), declined as the meal was consumed, and was lower (P < 0.05) in samples collected while the meals were being digested (0.41 microgram gentamicin/mL). Protein content was negatively correlated with antibacterial activity, with protein secretion lower (mg/mL and /min) before feeding, with an increase as the pigs ate and digested the meals (P < 0.05). The results indicate that the antibacterial activity in pancreatic juice is not secreted in parallel with protein secretion, suggesting that regulation involves alternative signaling pathways or contrasting responses to shared signals.     

The effect of pancreatic enzyme supplementation in patients with steatorrhoea after total gastrectomy.

OBJECTIVE: To assess the influence of pancreatic enzyme supplementation on symptoms, energy intake, bowel habits, and fat malassimilation in patients after total gastrectomy. DESIGN: A prospective, double-blind, randomized, parallel, placebo-controlled, multi-centre trial. SETTING: Institutionalized patients in three gastroenterological rehabilitation clinics. PARTICIPANTS: 52 institutionalized patients with a faecal fat output > or = 14 g/day, operated on for malignant gastric disease a median of 198 days (interquartile range (IQR) 47-608) previously, and free from recurrence and/or metastasis. INTERVENTIONS: Nine sachets of pancreatic enzymes per day (each containing lipase 36,000, amylase 27,000, protease 2400 FIP (Federation International Pharmaceutique)) or identical-looking placebo were given for 14 days. MAIN OUTCOME MEASURES: Abdominal symptoms, energy intake, bowel habits and fat malassimilation. RESULTS: After treatment, patients on enzyme therapy felt better overall (P = 0.006), but no improvement of a specific symptom could be identified. During the intervention, the median kilojoule intake per kilogram body weight was 9% higher in the placebo group (170.8 (IQR 146.9-202.6)) than in the enzyme-treated group (157.0 (IQR 134.8-170.4)) (P = 0.03). Enzyme treatment did not result in a significant difference between the placebo and the enzyme-treated group regarding bowel habits or fat malassimilation. CONCLUSIONS: The effect of high-dose pancreatic enzymes supplementation on symptoms and steatorrhoea after total gastrectomy is marginal and does not justify its routine use.     

Development of acute pancreatitis in rats after single ethanol administration and induction of a pancreatic juice edema

The effect of an acute gastral ethanol application and an additional induction of a pancreatic juice edema by an obstruction/hyperstimulation mechanism was studied in rats. Neither ethanol administration nor the combination of ductal obstruction and secretory stimulation resulted in an acute pancreatitis when applied independently. A combination of these factors, however, led to the development of AP in two-thirds of the rats treated in this manner. Its severity was evaluated by the degree of extrapancreatic fat necrosis, the increase in serum amylase and lipase activities, and by histologic investigations. It is assumed that a pancreatic juice edema, provoked by pancreatic secretion at temporary ductal obstruction, could be an important cofactor in formation of ethanol-induced acute pancreatitis.     

Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients with chronic pancreatitis

Background—The predominace of secretory IgA(S-IgA) in intestinal secretions compared with blood is wellestablished, but concentrations of this protein in pancreatic juice andits origin, especially in chronic pancreatitis, are unknown.
Aims—To investigate the role of S-IgA in chronic pancreatitis.
Patients—Twenty one patients with chronicpancreatitis (group I), three patients with proven malignancies (groupII), and 12 patients without pancreatic disease (group III).
Methods—Pure human pancreatic juice was collectedendoscopically in four fractions after consecutive stimulation withsecretin and cholecystokinin (CCK). Samples were analysed for S-IgA,protein, trypsinogen, and proteolytic activity.
Results—The S-IgA level was significant increasedin fraction 1 of pancreatic juice of group I (1210 (1411) ng/ml)compared with controls (33 (70) ng/ml). Protein concentrations andtrypsinogen content were lower in group I than in the other groups.Proteolytic activity could be observed in 53% of all 133 pancreaticjuice samples, but in 87% of fraction 1. In pancreatic tissue of three patients with chronic pancreatitis both IgA and secretory component were detected by immunohistology. Expression of the secretory componentby human pancreatic epithelial cells was increased in patients withchronic pancreatitis compared with normal controls. The concentrationof S-IgA in pancreatic juice did not correlate with the serum S-IgAlevel. In contrast, serum levels of S-IgA were decreased in patientswith chronic pancreatitis.
Conclusion—There are high levels of S-IgA inhuman pancreatic juice following chronic inflammation and a protectiverole is suggested for this immunoglobulin.

Keywords:chronic pancreatitis; pancreatic juice; proteaseactivity; protease inhibitors; secretory IgA; immunohistochemistry

     

Molecular forms of serum pancreatic stone protein in acute pancreatitis.

CONCLUSION: Elevation of serum pancreatic stone protein-(PSP) S1 suggests activation of trypsinogen in the pancreas. This information would prompt the start of intensive treatment and may improve prognosis of acute pancreatitis (AP). BACKGROUND: PSP exists in two molecular forms, PSP-S2-5 and PSP-S1. PSP-S1 is produced by enzyme cleavage of PSP-S2-5 by trypsin. Total serum PSP rose in AP, but little is known about its molecular forms. In this study, we characterized the molecular forms of serum PSP in AP. METHODS: Sera were taken from 8 patients with severe acute pancreatitis (sAP) and from 11 patients with mild acute pancreatitis (mAP). Serum PSP was characterized by high-performance liquid chromatography (HPLC) followed by the specific enzyme immunoassay (EIA). RESULTS: The total serum PSP in sAP was higher than in mAP, but the difference was not significant. The PSP-S1 was detected in serum in all (7/7) patients in sAP and in 72% (8/11) of patients in mAP. Serum level of PSP-S1 was significantly higher in sAP than that in mAP (p < 0.05), and the cutoff value to distinguish the two groups was 30 ng/mL. Serum PSP-S1 did not show significant correlation with total PSP, immunoreactive trypsin, or C-reactive protein.