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).     

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).     

Plasma concentrations of neurotensin and CCK in patients with chronic pancreatitis with and without enzyme substitution.

The peptide hormones neurotensin (NT) and cholecystokinin (CCK) are commonly attributed with a physiological role in the stimulation of exocrine pancreatic secretion. However, on the other hand, little is known about the effect of diminished exocrine pancreatic function and of the resulting maldigestion on postprandial plasma levels of these two gastrointestinal peptides. We investigated, therefore, the effect of enzyme substitution therapy on the magnitude and time course of plasma concentrations of both hormones in patients suffering from severe chronic pancreatitis. Pancreatic insufficiency led to elevated NT-concentrations, in response to a standard meal, which could be reduced by enzyme replacement therapy. Prior to enzyme therapy, the mean integrated postprandial release of NT amounted to 2800 +/- 250 pg/ml after 60 min in patients with severe chronic pancreatitis. This amount was significantly reduced to 1250 +/- 150 pg/ml after 60 min after enzyme therapy, compared to 810 +/- 90 pg/ml after 60 min in healthy volunteers after the standard meal. The integrated postprandial CCK level in patients investigated was significantly lower (35 +/- 4.8 pmol/L after 60 min) without any substitution therapy, compared to the integrated peptide amount in healthy volunteers (145 +/- 13.5 pmol/L after 60 min). Enzyme therapy in patients suffering from chronic pancreatitis led to an increased postprandial CCK-level (80 +/- 9.6 pmol/L after 60 min). Elevated CCK-plasma concentrations have not been demonstrated in these patients with pancreatic insufficiency. We therefore suggest that CCK might not play a major role in feedback regulation in patients with chronic pancreatitis. However, in light of elevated NT plasma concentrations in patients with chronic pancreatitis, NT-mediated influence on the pancreas deserves further study.     

Gallbladder dynamics in chronic pancreatitis

Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24–56 years) and 12 control subjects (4 females, 8 males, 21–50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (–30, –15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval.Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT<1.8 g/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3±3.1 cm³) as compared to controls (20.5±1.2 cm³) (P<0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8–46%) following ceruletide and from 17 to 86% (controls: 27–80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P<0.01). Postprandial PP response in CP was correlated with the PLT result (r=0.78;P<0.01) but not with gallbladder emptying or refilling time. We conclude that gallbladder emptying and refilling following the oral administration of a test meal or the stimulation with a pharmacological dose of ceruletide is normal in patients with chronic pancreatitis. Postprandial gallbladder emptying is not influenced by the degree of exocrine pancreatic insufficiency.     

Pancreatic trophism following colectomy in rats: the potential role of gastrointestinal hormones

It has been shown that the large bowel contains substances with a potential to inhibit exocrine pancreatic function. Following large bowel removal in rats, there is an increase of pancreatic weight, digestive enzyme concentration, and secretion capacity in vitro. To evaluate the role of various GI hormones in the exocrine pancreatic adaptation following colectomy, we measured plasma cholecystokinin (CCK), neurotensin, glucagon, and insulin after meal stimulation. The test meal was applied via a transabdominal gastric tube in eight colectomized Wistar rats after a median of 18 days following surgery. Ten rats with a gastric tube without previous bowel surgery served as controls. After large bowel removal, there was impaired glucose tolerance and attenuated plasma insulin secretion. Baseline plasma glucagon levels were increased after colon removal, whereas the total postprandial glucagon release was decreased. Baseline and postprandial neurotensin values were comparable in both the experimental and control animals. Baseline and postprandial CCK plasma levels were intensely increased in the colectomized rats. It is assumed that the baseline and postprandial CCK pattern in rats after subtotal colectomy is responsible for exocrine pancreatic adaptation.     

Pancreatic exocrine secretion and plasma gut hormones response after intraduodenal infusion of elemental diet in patients with chronic pancreatitis

We studied the responses of pancreatic polypeptide (PP) and cholecystokinin (CCK) using specific RIAs, and simultaneously exocrine pancreatic secretion and gall bladder contraction were checked by using triple lumen tube to intraduodenal ingestion of 100 Kcal/hr semi-digested liquid meal: Clinimeal (Eisai, Tokyo) or Elemental Diet: ED (Morishita, Osaka) in 10 patients with chronic pancreatitis (CP). Intraduodenal infusion of Clinimeal did not result in a significant physiological rise of CCK and PP from the basal values. Pancreatic secretions (volume and bicarbonate output) were slightly increased paralleled to the gall bladder contraction in chronic pancreatitis. On the other hand, intraduodenal ED can significantly stimulate the release of CCK from the small intestine and PP from the pancreas with the near range of physiological concentration. This level of CCK can evoke a significant increase in pancreatic secretion and gall bladder contraction. These results suggest that in CP the physiological regulation was disturbed and pancreatic secretion was not observed after ordinary meal ingestion. Infusion of ED which contained similar components of digestive product partially improved the responses of gut hormones and pancreatic secretion. Therefore, impaired gut hormone release in CP primarily is due to the inappropriate stimuli because of pancreatic exocrine dysfunction, and not other factors(s).     

Postprandial release of cholecystokinin after duodenum-preserving total pancreatectomy is independent of intraluminal pancreatic protease activity in dogs

The effect of meal stimulation, with and without the intraduodenal presence of pancreatic enzymes, on plasma cholecystokinin (CCK) release was studied in order to investigate the role of CCK in the putative feedback mechanism between intraduodenal pancreatic proteases and pancreatic enzyme secretion. Plasma CCK concentrations in response to a semiliquid meal, with and without the supplementation of exocrine pancreatic enzymes, were measured in 8 dogs after duodenum preserving pancreatectomy. With a well-balanced endocrine and exocrine substitution regimen all dogs were kept in good clinical condition, without steatorrhea or significant weight loss, and fasting plasma glucose levels within the normal range. Exocrine supplementation was stopped at least 3 days prior to tests. Basal plasma CCK levels after 3 days without exocrine supplementation (2.5 +/- 0.3 pM) did not significantly differ from the results with supplementation (3.0 +/- 0.5 pM) nor from the preoperative levels (2.3 +/- 0.3 pM). In addition, integrated plasma CCK responses to the meal without exocrine supplementation (330 +/- 37 pM.90 min) were not significantly different from the responses to the meal with exocrine supplementation (303 +/- 49 pM.90 min), or from the postprandial CCK response in the dogs with an intact pancreas preoperatively (390 +/- 100 pM.90 min). It is concluded that the release of CCK in dogs after total pancreatectomy is independent of intraluminal protease activity. It is therefore not likely that CCK mediates the putative feedback mechanism between intraluminal protease activity and pancreatic enzyme secretion in dogs.     

Plasma pancreastatin responses after intrajejunal infusion of liquid meal in patients with chronic pancreatitis

The plasma concentrations of pancreastatin and cholescystokinin (CCK), exocrine pancreatic responses, and gallbladder contraction following intrajejunal ingestion of 100 kcal/hr semidigested liquid meal (Clinimeal) were simultaneously studied in six controls and six patients with chronic pancreatitis. An intrajejunal infusion of Clinimeal resulted in significant rises of pancreastatin and CCK, which paralleled the pancreatic secretion and gallbladder contraction. On the other hand, an intrajejunal infusion of Clinimeal resulted in a delayed rise of pancreastatin and no rise of CCK in chronic pancreatitis. Pancreatic secretion did not increase, and gallbladder contraction was not induced in these patients. It is suggested that pancreastatin may play an important role in the regulation of intestinal phase of exocrine pancreas. The impaired pancreastatin and CCK release in chronic pancreatitis may be due to the inappropriate stimuli in the lumen, which is attributed to pancreatic exocrine dysfunction, or to disturbed physiological regulation between the pancreas and gastrointestinal tract.     

Postprandial gastric function in pancreatic insufficiency.

Abnormalities in postprandial gastric function could contribute to the maldigestion of pancreatic insufficiency. To measure simultaneously postprandial gastric secretion and emptying and correlate these measurements with intraluminal duodenal changes, we performed intestinal intubation and duodenal perfusion during feeding of a solid-liquid test meal in 10 healthy controls and 10 patients with documented pancreatic insufficiency before and after replacement therapy. In pancreatic insufficiency, intraduodenal pH was significantly decreased late in the postprandial period while simultaneously measured duodenal acid loads were normal, confirming that reduced bicarbonate output rather than increased acid delivery was responsible for higher duodenal acidity in these patients. Significant (P less than 0.05) reductions in postprandial acid, pepsin, and total secretory outputs were noted in untreated patients only during the first postprandial hour. Absolute gastric emptying rates were lower in patients (P less than 0.05) than in healthy subjects, but fractional rates of emptying were similar. Fasting and postprandial hypergastrinaemia were consistently observed in the patients with pancreatic disease. There are postprandial disturbances of secretory function but no primary gastric motor defect in patients with exocrine pancreatic insufficiency.     

Pancreatic polypeptide response in patients with chronic pancreatitis

We studied the plasma pancreatic polypeptide (PP) response to a meal in patients with pancreatitis and attempted to correlate the PP increment with the degree of pancreatic exocrine insufficiency. Control subjects and patients with recurrent pancreatitis showed significant mean increase (P<0.05) in plasma PP concentration in response to food. By contrast chronic pancreatitis patients had no significant increase in plasma PP. However, some subjects with normal pancreatic secretion had no response and some patients with chronic pancreatitis did show a response. In addition, no correlation was observed between the PP response and pancreatic exocrine secretion. We conclude that the PP response to a meal has only limited value in the detection of pancreatic destruction.     

Plasma CCK levels in patients with pancreatic insufficiency

After stimulation with a Lundh test meal, plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and output of pancreatic enzymes were measured in 33 patients with exocrine pancreatic insufficiency and 26 healthy subjects. Patients with impairment of pancreatic function were subdivided into those with moderate and severe insufficiency. Plasma CCK and PP were measured by radioimmunoassay. Fasting plasma CCK in patients with pancreatic insufficiency (5.8±1.1 pmol/liter) did not differ significantly from controls (4.2±0.6 pmol/liter). After endogenous stimulation with a Lundh meal, plasma CCK increased in both groups without significant differences over 2 hr. Basal and stimulated plasma levels of pancreatic polypeptide (PP) were markedly decreased only in patients with severe pancreatic insufficiency. Our results demonstrate that basal and meal-stimulated CCK levels in patients with pancreatic insufficiency do not differ from controls. Furthermore the extent of functional impairment of the exocrine pancreas did not influence basal and postprandial CCK release.     

Effects of ethanol on meal-stimulated secretion of pancreatic polypeptide and cholecystokinin: Comparison of healthy volunteers,heavy drinkers,and patients with chronic pancreatitis

Tiscornia and Dreiling (Physiopathogenic Hypothesis of Alcoholic Pancreatitis: Supranormal Ecbolic Stimulation of the Pancreon Units Secondary to the Loss of the Negative Component of Pancreas Innervation. Pancreas 1987;2:604–612.) proposed that hypertonicity of intrapancreatic cholinergic neurons provoked by chronic alcoholism may contribute to the pathogenesis of chronic pancreatitis (CP). In the present study, the validity of this hypothesis was investigated in humans by studying the effects of atropine, cisapride, and ethanol on the meal-stimulated secretion of pancreatic polypeptide (PP) and cholecystokinin (CCK) in healthy volunteers, heavy drinkers, and CP patients. In healthy volunteers, the early phase PP response (0–40 min) to a test meal was completely blocked by atropine, whereas it was augmented by cisapride, an enhancer of acetylcholine release from cholinergic nerves. The early phase PP response to a test meal was inhibited by ethanol in healthy volunteers, whereas, in heavy drinkers, the response was augmented and the inhibition by ethanol was abrogated. In CP patients, ethanol tended to enhance the early phase PP response. Ethanol did not affect the early phase CCK response to a test meal in any group, but it significantly enhanced the late phase CCK response (40–120 min) in CP patients. These results suggest that: (i) oral ethanol may inhibit the post-prandial activation of the cholinergic neural pathway to the pancreas in healthy subjects, (ii) in heavy drinkers, postprandial cholinergic tone may be augmented and become resistant to the inhibition by ethanol, and (iii) the ethanol-induced increase in the postprandial CCK response in CP patients may play some role in the pathophysiology of this disease.     

Atropine enhances food-stimulated CCK secretion in the rat

The effect of atropine on plasma cholecystokinin (CCK) and pancreatic secretion during intraintestinal infusion of a conventional defined formula liquid diet (Ensure HN, Ross Laboratories, 1.06 kcal/ml) was studied in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice, which were returned to the duodenum at all times. Pancreatic secretion was monitored during intraduodenal infusion of 0.15 M NaCl for 2 h followed by Ensure HN, both infused at 4.62 ml/h. Rats were infused i.p. with atropine (500 micrograms/kg/h) or vehicle throughout the experiment, beginning 1 h before monitoring of basal pancreatic secretion. Basal and 15 min postprandial plasma CCK concentrations were determined by bioassay. Atropine inhibited basal pancreatic protein secretion by approximately 60%. However, protein secretion during infusion of the diet was not decreased by atropine, due to a larger incremental pancreatic protein secretory response in atropine-treated rats. Plasma CCK 15 min after beginning the diet infusion was significantly increased by atropine (8.09 +/- 1.77 pM in atropine-treated rats versus 3.14 +/- 0.64 pM in controls). The results indicate that rats compensate for loss of cholinergic input to the pancreas by increasing CCK release in response to a meal. This is hypothesized to occur by virtue of reduced feedback inhibition of CCK release due to anticholinergic reduction of basal levels of intestinal protease activity.     

Interdigestive and postprandial duodenal pH in healthy probands, in patients with ulcer and in chronic pancreatitis

In patients with chronic pancreatitis (48), gastric ulcer (6), duodenal ulcer (6) and controls (12) duodenal pH was measured continuously by a glass electrode before and 90 minutes after a standard meal. The capacity of the stomach to secrete acid was known in all test persons, the degree of exocrine pancreatic insufficiency was determined according to the results of the S-CCK-test: 6 had no, 29 moderate and 13 severe pancreatic insufficiency. There were no significant differences between the mean interdigestive duodenal pH of the groups. After a meal, however, even patients with a normal pancreatic function but with hyperchlorhydria had a significantly lower pH (mean pH 5.5) than those with normo-chlorhydria (mean pH 6.1) and hypochlorhydria (mean pH 6.5). In patients with severe pancreatic insufficiency and normo-/hyperchlorhydria duodenal pH was much lower (mean pH 4.2) in some cases to pH 3.5, thus well below a level known as inactivating pancreatic enzymes. The total duration of the pH being less than 4.5 amounted to 12% of the postprandial measuring time (11 of 90 min). If, however, severe pancreatic insufficiency was combined with a-/hypochlorhydria duodenal pH did not differ from controls. Thus, reduced acid secretion of the stomach exerts beneficial effect on duodenal pH in patients with severe pancreatic insufficiency.     

Advances in nutritional management of chronic pancreatitis

Nutrition has an important role in the management of chronic pancreatitis (CP), with two main goals for treatment of patients. The first goal is to provide optimal nutrition support and the second is to decrease pain by minimizing stimulation of the exocrine pancreas. Because cholecystokinin (CCK) stimulates secretion from the exocrine pancreas, one approach is to decrease CCK levels through modulation of diet. If postprandial pain is a limiting factor, alternative enteral therapies that minimally stimulate the pancreas may be beneficial. Nutritional counseling, antioxidants, and pancreatic enzymes may play a role in effective management of CP as well. In addition, because idiopathic CP is associated with cystic fibrosis gene mutations, therapies directed toward cystic fibrosis may also benefit these patients.     

Pancreatic polypeptide release stimulated by food, secretin and cholecystokinin in chronic pancreatitis

The pancreatic polypeptide (PP) release after a standard meal and the PP release and the pancreatic secretion of bicarbonate and amylase after stimulation by secretin GIH, 1 CU kg-1 intravenously, and by cholecystokinin (CCK), 1 Ivy dog unit kg-1 intravenously, have been investigated in 10 patients with chronic pancreatitis. Significant correlations were found between the integrated PP responses after food and hormonal stimulation (p less than 0.05), between the integrated PP response and the peak serum PP concentration after food (p less than 0.01) and after secretin/CCK (p less than 0.01), and between the peak serum PP concentrations obtained after food, secretin, and CCK (p less than 0.01). The pancreatic outputs of bicarbonate and amylase and the peak amylase concentration after hormonal stimulation were significantly correlated (p less than 0.01), but no significant correlation was found between any one of these variables of exocrine pancreatic function and the PP release. It is concluded that, in chronic pancreatitis, food, secretin, and CCK stimulate PP release similarly and that no correlation can be established between the PP release and the exocrine pancreatic secretion.     

Dissociation of cholecystokinin and pancreaticobiliary response to intraduodenal bile acids and cholestyramine in humans

The role of intraduodenal bile acids in the regulation of cholecystokinin (CCK), pancreatic polypeptide (PP), and secretin as well as exocrine pancreatic and biliary secretion was investigated by means of a duodenal marker perfusion technique in volunteers. The following solutions were perfused: (1) liquid test meal, (2) test meal with 6 g cholestyramine, (3) test meal with 2 g chenodeoxycholic acid (CDC), (4) test meal with 6 g cholestyramine and 2 g CDC, (5) 6 g cholestyramine alone, and (6) 2 g CDC alone. The test meal caused an immediate increase in CCK and PP plasma levels, whereas secretin was not significantly altered. CCK release was further enhanced by addition of cholestyramine, whereas CDC inhibited release. The stimulatory effect of cholestyramine was abolished by CDC. CDC alone and in combination with the test meal stimulated secretin release. The response of PP to the test meal was not altered by addition of either compound. Cholestyramine and CDC alone caused only a very small increase in CCK levels, whereas PP was stimulated to nearly postprandial values. Meal-stimulated pancreatic and biliary secretion was significantly enhanced by cholestyramine, CDC, and the combination of both. CDC and cholestyramine alone each stimulated enzyme and bile secretion to a greater extent than the test meal. We conclude that intraduodenal bile salts are a modulator of postprandial CCK release. Changes in exocrine pancreatic and biliary and PP secretion do not necessarily parallel CCK concentrations, suggesting that different mediators are involved in the observed bile acid-induced changes in humans.     

On the role of gastrin-releasing peptide in meal-stimulated exocrine pancreatic secretion.

The contribution of gastrin-releasing peptide (GRP) in the physiologic pancreatic response to a meal is unknown. We therefore investigated whether immunoneutralization of GRP could influence the exocrine pancreatic response to a meal as well as plasma concentrations of the peptide hormones neurotensin (NT) and cholecystokinin (CCK). Modified Herrera fistulas were implanted in five mongrel dogs. After a standard meal, we analyzed plasma NT, CCK, and GRP, and protein and enzyme (amylase, lipase, trypsin) content of exocrine pancreatic juice. An unspecific rabbit immunoglobulin solution was administered intravenously as a control. This experiment was repeated with a specific anti-GRP-immunoglobulin. The i.v. administration of the anti-GRP-antibody significantly inhibited meal-stimulated pancreatic secretion. Integrated protein output decreased from 58.4 to 36.8 g/180 min (p < 0.05), as did amylase (2,102 to 1,145 KU/180 min; p < 0.05), lipase (2,258 to 1,172 KU/180 min; p < 0.05), and trypsin (5,321 to 4,990 U/180 min). Postprandially released NT decreased from 8,271 to 5,825 pmol/180 min (p < 0.05). In contrast, integrated amounts of CCK remained relatively stable with 473 to 611 pmol/180 min. The neuropeptide GRP is one of the biologically important regulatory factors influencing meal-stimulated pancreatic secretion, as well as the postprandial plasma level of the peptide hormone NT in the dog. These mentioned effects of postprandially released GRP seem not to be mediated by CCK in an endocrine manner.     

Influence of extrinsic denervation of the pancreas on food-stimulated pancreas secretion and cholecystokinin and neurotensin release in the dog]

In the present study we examined the effect of extrinsic pancreatic denervation on meal-stimulated pancreatic exocrine secretion and the release of neurotensin and CCK in dogs. Denervation of the pancreas significantly decreased protein output from preoperatively 16,661 +/- 1824 mg x 150 min to 2033 +/- 316 mg x 150 min postoperatively (p less than 0.001), and bicarbonate secretion from 297.5 +/- 36 mmol x 150 min to 104.85 +/- 16 mmol x 150 min (p less than 0.01). Release of neurotensin and CCK was not altered by interruption of the extrinsic pancreatic nerves. Our findings are consistent with the hypothesis that pancreatic secretory response to a meal is predominantly mediated by neutral extrinsic reflexes.     

Comparison of loxiglumide, a cholecystokinin receptor antagonist, and atropine on hormonal and meal-stimulated pancreatic secretion in man

The effects of loxiglumide, a potent cholecystokinin (CCK)-receptor antagonist, and atropine, a muscarinic receptor blocker, on exocrine pancreatic secretion stimulated by hormones (secretin plus CCK) and a Lundh test meal were studied in healthy young volunteers. Loxiglumide infused intravenously in gradually increasing doses (2-16 mumol/kg-h) caused a dose-dependent inhibition of pancreatic enzyme secretion induced by intravenous infusion of a constant dose of secretin (82 pmol/kg-h) plus CCK-8 (85 pmol/kg-h) but had relatively smaller influence on duodenal volume flow and bicarbonate output. Atropine (20 nmol/kg) also caused a significant reduction in pancreatic enzyme secretion but failed to affect the volume flow or bicarbonate secretion induced by secretin plus CCK, possibly owing to the high doses of secretin and CCK used in these tests. Both loxiglumide and atropine inhibited the pancreatic enzyme response to a Lundh meal, but atropine was more effective in the early phase and loxiglumide in the late phase of the postprandial secretion. Neither loxiglumide nor atropine affected the plasma gastrin and CCK levels, but both antagonists reduced plasma pancreatic polypeptide responses to the Lundh meal. We conclude that 1) loxiglumide results in a relatively stronger suppression of the pancreatic enzyme than aqueous-alkaline secretion induced by secretin plus CCK, whereas atropine inhibits only enzyme secretion; and 2) both loxiglumide and atropine suppress the pancreatic enzyme responses to the meal stimulation without affecting the postprandial plasma gastrin and CCK responses.