Postprandial Pancreatic Secretion Research Articles

Obesity is associated with impaired postprandial pancreatic polypeptide secretion.

This study aims to compare the levels of serum pancreatic polypeptide (PP), insulin (INS), C-peptide (C-P), and glucagon (GCG) before and after glucose stimulation in type 2 diabetes mellitus (T2DM) patients with different body mass indexes (BMI), analyze the relevant factors associated with PP secretion, and further investigate the role of PP in the development of obesity and diabetes. Data were collected from 83 patients from the hospital. The subjects were divided into normal-weight group, overweight group, and obese group according to their BMI. All subjects were tested with the standard bread meal test (SBMT). PP and relevant parameters were measured, and the area under the curve (AUC) was calculated after 120min of SBMT. AUCpp (AUC of PP) was used as the dependent variable, and the potential influencing factors were used as independent variables for multiple linear regression analysis. The obese and overweight groups had significantly lower PP secretion than the normal-weight group (485.95 pg·h/ml, 95% CI 76.16-895.74, p = 0.021; 664.61 pg·h/ml, 95% CI 285.46-1043.77, p = 0.001) at 60min postprandial. PP secretion in the obese and overweight groups was also significantly lower than that in the normal-weight group (520.07 pg·h/ml, 95% CI 186.58-853.56, p = 0.003; 467.62 pg·h/ml, 95% CI 159.06-776.18, p = 0.003) at 120min postprandial. AUCpp was negatively associated with BMI (r = -0.260, p = 0.017) and positively associated with AUCGCG (r = 0.501, p< 0.001). Multiple linear regression analysis showed that there was a linear correlation between AUCGCG, BMI, and AUCpp (p< 0.001, p = 0.008). The regression equation was calculated as follows: AUCpp = 1772.255-39.65 × BMI + 0.957 × AUCGCG (R2=54.1%, p< 0.001). Compared with normal-weight subjects, overweight and obese subjects had impaired PP secretion after glucose stimulation. In T2DM patients, PP secretion was mainly affected by BMI and GCG. The Ethics Committee of the Affiliated Hospital of Qingdao University. http://www.chictr.org.cn, identifier ChiCTR2100047486.

Impaired glucose tolerance is associated with enhanced postprandial pancreatic polypeptide secretion

BackgroundThe purpose of this study is to compare serum pancreatic polypeptide (PP), insulin, C‐peptide, and glucagon in different glucose tolerance stages; analyze the influencing factors of PP secretion; and further explore the role of PP in the pathogenesis of diabetes mellitus.MethodsData were collected from 100 subjects from hospital. According to the results of oral glucose tolerance test (OGTT), the subjects were divided into a normal glucose tolerance (NGT) group, an impaired glucose regulation (IGR) group, and a newly diagnosed type 2 diabetes mellitus (T2DM) group. PP and the related parameters were measured, and the area under the curve (AUC) 120 min after OGTT was calculated. AUCpp (AUC of PP) was used as the dependent variable and the potentially influencing factors were used as the independent variable for multiple linear regression analysis.ResultsPostprandial 60 min PP in the IGR group was higher than those in the NGT group (2973.80 [±547.49] pg·h/mL vs 2663.55 [±594.89] pg·h/mL, p < 0.05). AUCpp was significantly higher in the IGR group (428.76 pg·h/mL, 95% confidence interval [CI] [41.06 –816.46], p = 0.031) and newly diagnosed T2DM group (404.35 pg·h/mL, 95% CI [5.37–803.33], p = 0.047) than in the NGT group. AUCpp was negatively correlated with body mass index (BMI) (r = −0.235, p = 0.038) and positively correlated with postprandial 60 min blood glucose (r = 0.370, p = 0.001) and AUCbg (AUC of blood glucose) (r = 0.323, p = 0.007). Multiple linear regression analysis indicated that there was a linear correlation between BMI, AUCbg, and AUCpp (p = 0.004, p = 0.001), and the regression equation was calculated as: AUCpp = 6592.272 + 86.275 × AUCbg‐95.291 × BMI (R2 = 12.7%, p < 0.05).ConclusionsCompared with NGT subjects, IGR and T2DM patients have an enhanced postprandial PP secretion. In T2DMs, the secretion of PP is mainly affected by BMI and blood glucose.

Secretin

This review describes the history of secretin discovery, identification, purification, and structural determination; cloning of secretin and its receptor; synthetic secretin; and highly specific and sensitive radioimmunoassay to define the characteristic physiological role on postprandial pancreatic fluid and bicarbonate secretion, which requires robust potentiation by cholecystokinin. Secretin plays a key role in the negative and positive regulatory mechanisms of exocrine pancreatic secretion. Secretin-releasing peptides were discovered in duodenal acid perfusates of both rat and dog and in canine pancreatic juice. The release and action of secretin and secretin-releasing peptides are in part mediated via vagovagal reflex mechanism involving afferent sensory neurons in proximal intestine and efferent cholinergic neurons in the pancreas. Besides acetylcholine, many neurotransmitters or neuromodulators influence release and action of secretin. The action of secretin in the pancreas depends on insulin, which also suppresses local release of somatostatin and pancreatic polypeptide. Thus, release and action of secretin are mediated via neurohormonal interaction. Clinical conditions with hypersecretinemia and hyposecretinemia are discussed. Synthetic human secretin is used for studies of exocrine pancreatic secretion, secretin-enhanced magnetic resonance cholangiopancreatography combined with exocrine pancreatic function test and diagnosis of gastrinoma syndrome. Therapeutic use of secretin is considered for the relief of severe pain in chronic pancreatitis.

Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder

Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD). We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients. The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations. Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain-gut axis.

Dietary sodium butyrate supplementation increases digestibility and pancreatic secretion in young milk-fed calves

The aim of this study was to test, in 8 calves fed milk formula based on soybean protein, the ability of sodium butyrate (SB) supplementation to improve nutrient digestibility and daily pancreatic secretions and to modify the kinetics of these secretions. Additionally, effects of duodenal SB infusion were evaluated. Plasma levels of gastrin, secretin, and cholecystokinin were measured. Butyrate supplementation in milk formula increased nutrient digestibility and total daily pancreatic secretions. For juice volume, this increase was most important from 12 to 17h after the morning meal. During the 3-h postprandial period, oral SB supplementation reduced the physiological decrease of postprandial pancreatic secretion (while duodenal digesta flow rate was maximal) and had a minor effect on plasma gut regulatory peptide concentrations. Compared with the diet without SB, ingestion of SB stimulated pancreatic secretion. Taken together, these results could explain the measured increase in nutrient digestibility. The data obtained after duodenal SB infusion did not indicate an effect on pancreatic secretion, apart from elevated lipase output compared with control. The mechanisms responsible for these events are not known and circulating gut regulatory peptides do not seem to be implicated. Our work brings new results regarding SB as a feed additive in young calf nutrition.

Glucose-dependent insulinotropic polypeptide stimulates the proliferation of colorectal cancer cells

Although numerous epidemiological studies have provided convincing evidence for an increase in the prevalence of colorectal cancer (CRC) in obese individuals, the precise mechanisms involved have not been elucidated. Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal regulatory peptide whose primary physiologic role is to stimulate postprandial pancreatic insulin secretion. Like insulin, GIP has been linked to enhanced nutrient efficiency, which occurred during the course of evolution. Its expression is increased in obesity, and we thus initiated studies to examine whether GIP might contribute to the pathogenesis of obesity-related CRC. RT-PCR and Western analysis demonstrated the presence of the GIP receptor (GIPR) in several human CRC cell lines. GIP stimulated the proliferation of MC-26 cells, a mouse CRC cell line, in a concentration-dependent manner. Western analysis showed that GIP induced the activity of several downstream signaling molecules known to be involved in cellular proliferation in a concentration- and time-dependent manner. These studies indicate that the presence of GIP receptors in CRC may enable ligand binding and, in so doing, stimulate CRC cell proliferation. The overexpression of GIP, which occurs in obesity, might thereby be contributing to the enhanced rate of carcinogenesis observed in obesity.

Postprandial physiology and the pathogenesis of type 2 diabetes mellitus

Background: Patients with type 2 diabetes mellitus (DM) have an increased risk of cardiovascular morbidity and mortality. Recent studies implicate postprandial hyperglycemia as an important driver of the increased risk of cardiovascular disease in patients with type 2 DM or prediabetes. Objectives: This article reviews the postprandial physiology of glucose and insulin, the role of postprandial hyperglycemia in the increased risk of cardiovascular disease in patients with type 2 DM, and the role of insulin and other agents in reducing that risk. Methods: Relevant articles for this review were identified through a search of MEDLINE (1999-2007; Englishlanguage articles only). The search terms used were glucose, insulin, pathophysiology, postprandial, hyperglycemia, and cardiovascular risk. Results: The concentration of glucose in plasma is determined by the relative rates of glucose entering and leaving the circulation. The rate at which intestinally absorbed glucose disappears from the circulation is controlled primarily by insulin. Insulin stimulates cells in insulin-sensitive tissue to increase uptake of glucose and acts directly on the liver to suppress hepatic glucose production and postprandial pancreatic a-cell secretion of the glucoregulatory hormone glucagon. Elevations of glucose in plasma may increase cardiovascular risk in several ways. Postprandial hyperglycemia has been shown to increase the production of free radicals and attenuate antioxidant defenses, activate prothrombotic pathways, induce vasoconstriction, and increase circulating levels of adhesion molecules. Postprandial hyperglycemia also has been correlated with carotid intima-media thickness, a surrogate marker for cardiovascular dysfunction. Insulin may reduce cardiovascular risk. Insulin is a known vasodilator that increases blood flow through the macrovasculature and microvasculature. It also appears to have direct anti-inflammatory effects, suppressing the generation of reactive oxygen species and proinflammatory transcription factors, as well as antiatherogenic effects, reducing postprandial hypertriglyceridemia, total atherosclerotic area, and number of aortic lesions. Conclusions: The adverse effects of postprandial hyperglycemia, together with the accompanying dyslipidemia, on cardiovascular health suggest that postprandial hyperglycemia should be a primary target of antidiabetic therapy. There is ample evidence to show that reducing postprandial hyperglycemia in patients with type 2 DM or prediabetes can reduce cardiovascular risk. Insulin may be an ideal agent for the treatment of postprandial hyperglycemia owing to its antihyperglycemic and cardioprotective effects.

Dietary Counseling Versus Dietary Supplements for Malnutrition in Chronic Pancreatitis: A Randomized Controlled Trial

Up to 50% of patients with chronic pancreatitis (CP) are malnourished. There are limited data on the role of dietary intervention in improving the nutritional status of such patients. The aim was to compare the efficacy of medium chain triglyceride (MCT)-enriched commercial dietary supplements with dietary counseling for homemade food in the management of malnutrition in patients with CP. In a randomized controlled trial, consecutive undernourished patients with CP (body mass index [BMI] <18.5 kg/m(2)) at a tertiary care hospital were randomized to receive either dietary counseling for regular homemade food or commercial MCT-enriched dietary supplements for a period of 3 months to compensate for the dietary calorie deficit. All patients received standard management for CP including pancreatic enzyme supplements. Primary outcome measure was improvement in BMI. Sixty malnourished patients with CP were randomized to counseling group (n = 29; mean age, 32 +/- 10 years; male, 83%) and supplementation group (n = 31; mean age, 28 +/- 10 years; male, 84%). BMI increased in both the counseling group and supplementation group (17.2 +/- 1.7 vs 18.1 +/- 1.8 kg/m(2), P = .001; 16.7 +/- 1.6 vs 18.2 +/- 1.6 kg/m(2), P = .001). There were similar improvements in triceps skinfold thickness, dietary intake, fecal fat, and pain score during a period of 3 months in both groups. There was, however, no significant difference between the counseling and supplementation groups with regard to any of the outcome measures. Dietary counseling for a balanced homemade diet is as good as commercial food supplements in improving malnutrition in patients with CP.

The antagonistic metabolite of GLP-1, GLP-1 (9-36)amide, does not influence gastric emptying and hunger sensations in man

Objective. Glucagon-like peptide-1 (GLP-1 (7-36)amide) is an intestinal hormone that is released in response to meal ingestion. GLP-1 reduces postprandial gastric and exocrine pancreatic secretion and is believed to inhibit gastric emptying. Furthermore, GLP-1 may play a role in hunger and thirst regulation. In vivo, GLP-1 is rapidly (within minutes) converted into a metabolite, GLP-1 (9-36)amide, which has been shown to act as a GLP-1 receptor antagonist in vitro and in anaesthetized pigs. The purpose of this study was to assess the effect of infusion of GLP-1 (9-36)amide on hunger ratings and antral emptying of a meal. Material and methods. Six healthy volunteers were tested in a double-blind, placebo-controlled fashion. Antral emptying of a liquid meal and hunger ratings were determined using ultrasound technology and visual analogue scale scoring during infusions of saline or GLP-1 (9-36)amide (5 pmol/kg body wt/min) resulting in supraphysiological concentrations. Results. Infusion of GLP-1 (9-36)amide had no effect on gastric emptying or the sensation of hunger compared to saline. Conclusions. Our findings suggests that the rapid formation of the antagonistic metabolite does not influence gastric emptying and hunger ratings in humans even when it is present in supraphysiological concentrations.

Effects of Nitric Oxide Synthase Inhibitor on the Digestive System Measured by Simultaneous Monitoring of Gastric Motility, Gastric Emptying Activity and Postprandial Pancreaticobiliary Secretion in Dogs

Relationships between the NO synthase inhibitor and gastric and pancreaticobiliary functions measured simultaneously in the digestive state have been little studied. The aim of this study was to estimate the effect of NO synthase inhibitor on integrated digestive function in conscious dogs. A strain gauge force transducer was implanted on the gastric antrum of 6 mongrel dogs to measure gastric contractile activity and two duodenal cannulas were inserted into the proximal and distal sites to measure the gastric emptying rate and the pancreaticobiliary output into the duodenum using our novel method. Postprandial pancreatic and biliary secretion were presented as amylase and bile acid activity, respectively. Furthermore, a cervical cannula was placed into the superior vena cava as a route for the administration of NO synthase inhibitor, N omega-nitro-L-arginine (L-NNA), at a dose of 2.5 mg/kg-h. In a group given L-NNA, gastric contractile activity after ingestion was significantly enhanced, but the emptying rates of gastric solids and liquids were significantly suppressed in comparison with the control. The mean 0-1 h amylase integrated output was significantly (P < 0.05) decreased in comparison with the control, and the mean bile acid integration of 0-1 h output was also significantly (P < 0.01) decreased. A possible explanation for this observation is that smaller volumes of nutrient are delivered into the duodenum; however, it could also be that postprandial pancreaticobiliary secretion is inhibited by an alteration of blood flow or by a change in contractions of the sphincter of Oddi after the administration of L-NNA.

New insights into neurohormonal regulation of pancreatic secretion

The existence of high- and low-affinity cholecystokinin (CCK)-A receptors on rodent pancreatic acini is well established. Until recently, CCK was believed to act directly on pancreatic acini to stimulate pancreatic secretion in both rodents and humans. However, conclusive evidence that human pancreatic acini lack functional CCK-A receptors has been presented. Despite substantial differences in rodent and human pancreatic physiology, CCK appears to act via vagal cholinergic pathways to mediate pancreatic secretion in both species. Structural and functional evidence suggests that CCK acts on vagal afferent fibers, which may explain how CCK doses that produce physiologic plasma CCK levels act via vagal cholinergic pathways to stimulate pancreatic secretion. Although most knowledge of vagal CCK-A receptors comes from research on rodents, physiologic studies suggest that this information is applicable to humans. In contrast to its effect on satiety, which is mediated by low-affinity vagal CCK-A receptors, CCK acts through high-affinity CCK-A receptors to evoke pancreatic secretion, suggesting that different affinity states of the vagal CCK receptors mediate different digestive functions. Vagal afferent pathways also transmit sensory information about the mechanical and physiochemical state of the digestive tract, mediated in part by serotonin, which, in turn, influences pancreatic secretion. A synergistic interaction between CCK and serotonin at the level of the nodose ganglia may explain the robust postprandial pancreatic secretion despite a modest postprandial increase in plasma CCK. Important physiologically, these findings not only explain discrepancies in previous in vivo vs. in vitro studies, but they revolutionize our current concept of the mechanism of CCK on pancreatic exocrine secretion.

The role of cholinergic and peptidergic pathways in the regulation of pancreatic exocrine function during postnatal development in pigs.

The aim of this study was to investigate the role of the parasympathetic (cholinergic and peptidergic) nervous system in the regulation of exocrine pancreas function in piglets during their early postnatal development. The cholinergic and peptidergic regulatory pathways of exocrine pancreatic function were tested by the specific muscarinic receptor blocker 4-diphenylacetoxy-N-methylpiperidine-methiodide (4-DAMP) and bombesin, respectively. At the age of 2 weeks, piglets were surgically fitted with a chronic pancreatic duct catheter, a duodenal re-entrant cannula and a jugular vein catheter. The experiments comprised a pre-weaning period, and a post-weaning period that commenced at the beginning of the 5th week of age. Intravenous infusion of 4-DAMP (100 pmol x kg(-1) x h(-1)) reduced the outflow of pancreatic juice, the output of total protein and the activity of trypsin, chymotrypsin, carboxyl ester hydrolase and amylase during preprandial and postprandial pancreatic secretion, in both the pre- and post-weaning periods. However, the inhibitory effect of 4-DAMP during postprandial secretion was significantly greater (P < 0.05) in suckling piglets. The infusion of bombesin (10, 100 and 1000 pmol x kg(-1) x h(-1)) stimulated exocrine pancreatic secretion in a dose-dependent manner during both the pre- and post-weaning periods. However, the stimulatory effect of 1000 pmol x kg(-1) x h(-1) bombesin on total protein output and the activities of trypsin, chymotrypsin and amylase were significantly higher (P < 0.05) in suckling piglets. In summary, our study showed that cholinergic and peptidergic mechanisms are involved in the regulation of exocrine pancreas function in piglets in both the pre- and post-weaning stages. 4-DAMP had a greater inhibitory effect on exocrine pancreatic secretion in piglets during the pre-weaning period. Thus, these observations suggest that the parasympathetic nervous system plays a dominant role in the functioning of the exocrine pancreas at this time. The action of bombesin suggests that it is a potent secretagogue for the exocrine pancreas in pigs during their postnatal development.

Effect of Helicobacter pylori Infection on Gastrointestinal Motility, Pancreatic Secretion and Hormone Release in Asymptomatic Humans

Background: Helicobacter pylori infection is associated with complex alterations of the gastric physiology in patients with ulcer disease or functional dyspepsia. We aimed at evaluating whether H. pylori infection is accompanied by changes in interdigestive and postprandial gastrointestinal motility, exocrine pancreatic secretion or hormone release in asymptomatic subjects. Methods: Nineteen healthy men (age range 26-35 years) were studied after 12 h fasting. Motor activity was recorded for a complete motor migrating complex cycle and two postprandial hours. Pancreatic enzyme secretion was evaluated using a standard duodenal perfusion technique. Plasma concentrations of gastrin, PP and motilin were determined at 15-min intervals. H. pylori infection was proved by serology and 13C-urea breath test. Results: Eight subjects (42%) were H. pylori positive. Interdigestive and postprandial gastrointestinal motility were similar in H. pylori positive and negative subjects. Interdigestive pancreatic secretion was increased in H. pylori positive subjects ( P < 0.05). Postprandial pancreatic secretion tended also to be higher in H. pylori positive subjects. H. pylori infection was associated with an increased postprandial release of gastrin ( P < 0.05) as well as with a slight increase of interdigestive gastrin release. The release of PP and motilin, as well as the interdigestive coordination between gastrointestinal motility, pancreatic secretion and hormone release, was not altered by H. pylori infection. Conclusions: H. pylori infection in asymptomatic subjects is associated with changes not only in gastric physiology but also in pancreatic function. This first reported link between H. pylori and the pancreas could have pathophysiological implications in pancreatic diseases and therefore deserves further study.

Effects of intraduodenal administration of tarazepide on pancreatic secretion and duodenal EMG in neonatal calves

The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and the mechanism(s) involved in CCK-induced pancreatic secretion were studied in conscious calves. Seven 1-week-old calves were fitted with a pancreatic duct catheter, duodenal cannula and duodenal electrodes. Pancreatic exocrine secretion and duodenal EMG were studied following intraduodenal CCK-A receptor antagonist (Tarazepide), intravenous atropine, and intravenous or intraduodenal CCK-8 administrations. Tarazepide decreased duodenal electric activity, reduced interdigestive pancreatic secretion, especially protein; reduced cephalic and early postprandial (milk) induced secretion of bicarbonate and protein. Pancreatic protein secretion to intravenous CCK-8 was little affected by atropine, but was significantly reduced by Tarazepide±atropine; in contrast, protein secretion to intraduodenal CCK-8 was abolished by Tarazepide or atropine. We conclude that pre- and especially early postprandial pancreatic secretion are partly controlled via CCK-A (mainly mucosal) mediated mechanisms.

Role of serotonin pathway in the mediation of postprandial pancreatic enzyme secretion in humans

Role of serotonin pathway in the mediation of postprandial pancreatic enzyme secretion in humans

Duodenal secretion and fecal excretion of pancreatic elastase-1 in healthy humans and patients with chronic pancreatitis.

Fecal elastase-1 is a candidate for a sensitive noninvasive test detecting chronic pancreatitis. This prospective study enrolled 10 healthy male controls and 23 patients referred for tube testing of pancreatic function. It was designed (a) to correlate duodenal outputs and fecal concentrations of elastase-1 with duodenal outputs of amylase, lipase, trypsin, and chymotrypsin in the fed state (duodenal perfusion of a mixed liquid meal at 2.5 kcal/min for 150 min), (b) to compare the diagnostic accuracy of fecal elastase-1 and fecal chymotrypsin, and (c) to characterize the cyclical pattern of postprandial pancreatic secretion in healthy subjects and patients with chronic pancreatitis. Based on their enzyme responses to duodenal meal perfusion and imaging procedures, 12 patients were classified as having normal pancreatic function and 11 patients as having chronic pancreatitis. Duodenal enzyme outputs of elastase-1 were markedly lowered in chronic pancreatitis (p < 0.0001) and correlated well with the outputs of the other four enzymes (r > 0.71, p < 0.00001). Fecal concentrations of elastase-1 were also clearly reduced in chronic pancreatitis (p < 0.0001). Fecal chymotrypsin was less strongly associated with duodenal enzyme outputs (r = 0.33 to r = 0.587), whereas fecal elastase-1 correlated more precisely with the duodenal outputs of all five enzymes (r = 0.637 to r = 0.830, p < 0.00001). Sensitivity and specificity in the detection of chronic pancreatitis amounted to 0.64 and 0.95 for fecal elastase-1 and 0.27 and 0.95 for fecal chymotrypsin, respectively. In the postprandial state, peaks of enzyme secretion occurred at a frequency of about 1 peak/150 min. The amplitude but not the frequency of secretory peaks was markedly reduced in chronic pancreatitis (p < 0.01). We conclude that fecal elastase-1 clearly exceeds the sensitivity of fecal chymotrypsin in the diagnosis of chronic pancreatitis but does not reliably detect all cases with mild to moderate disease. The pattern of postprandial pancreatic secretion is cyclical, even with minimal secretory outputs in chronic pancreatitis.

Plasma Concentrations of Cholecystokinin and Neurotensin in Patients with Cystic Fibrosis

Background: Regulation of pancreatic exocrine secretion is controlled by vagovagal reflexes and hormones. A negative feedback control mechanism exists between the intraduodenal protease concentration and pancreatic enzyme secretion. In man cholecystokinin (CCK) is the major regulator of postprandial pancreatic enzyme secretion. There is a 50% reduction of meal-stimulated secretion by the specific CCK receptor antagonist loxiglumide, whereas atropine completely blocks postprandial secretion. Neurotensin is released postprandially by nerval reflexes and fat. It has been claimed that both hormones are increased in patients with pancreatic insufficiency. Methods: We investigated CCK and neurotensin levels in patients with cystic fibrosis and pancreatic insufficiency. In 35 patients (2–24 years old) with cystic fibrosis with steatorrhea and in 15 patients (1.5–24 years old) with cystic fibrosis without pancreatic insufficiency pre-and post-prandial CCK and neurotensin plasma levels were measured 3 days after pancreatic enzyme therapy had been withdrawn. Nine patients (3–14 years old) who had no complaint of abdominal disease served as controls. Results: Basal and postprandial CCK plasma levels did not differ statistically in the three groups, whereas basal and postprandial neurotensin levels were significantly increased in the cystic fibrosis groups. The severity of the disease had no effect on the neurotensin levels. Conclusions: Cystic fibrosis patients with severe pancreatic insufficiency did not have increased CCK plasma levels, suggesting that a CCK-mediated feedback mechanism of pancreatic enzyme secretion does not operate in our patients. In contrast, basal and postprandial neurotensin plasma levels were significantly increased in patients with cystic fibrosis but were independent of the severity of the pancreatic insufficiency.

Simultaneous observation of endocrine and exocrine functions of the pancreas responding to somatostatin in man

Six patients who underwent segmental autotransplantation of the caudal pancreas (SAT) following total pancreatectomy for pancreatic cancer were investigated. The graft was transplanted to the left groin, and pancreatic juice was diverted outside through a polyethylene tube indwelled into the main pancreatic duct. In these SAT patients, the responses of insulin (IRIS) in terms of plasma levels and pancreatic secretion to subcutaneous injections of somatostatin octreotide (Sandostatin ®: SMS201-995) were simultaneously observed. Four doses (0.039, 0.156, 0.625 and 2.5 μg/kg) of SMS201-995 were given on separate days. As a control, saline was injected subcutaneously. Standard liquid test meal was given 1 h after the subcutaneous injection. The basal plasma IRI were significantly decreased with doses greater than 0.156 μg/kg. The postprandial responses of IRI was also significantly suppressed with the same dosis. On the other hand, the basal pancreatic exocrine secretion was significantly suppressed with doses greater than 0.625 μg/kg. The postprandial pancreatic exocrine secretion was also significantly suppressed with doses greater than 0.625 μg/kg. Those suppressions were dose-dependent. The postprandial CCK secretion was also significantly suppressed in dose-dependent manner with SMS201-995. The CCK suppression was significantly correlated with the suppression of pancreatic exocrine secretion. This clinical study under the setting of SAT demonstrated not only the direct inhibitory effect of somatostatin on both the islet and acinar cells but also, probably, the indirect inhibitory effect on the acinal cells via suppression of CCK release in humans.

Effect of a wheat amylase inhibitor on canine carbohydrate digestion, gastrointestinal function, and pancreatic growth

Background/Aims : Chronic amylase inhibition might be useful to treat diabetes mellitus and obesity. Duodenal and ileal cannulas were placed in 8 dogs to determine if long-term ingestion of a wheat amylase inhibitor maintained amylase inhibition or affected gastrointestinal or metabolic function or pancreatic growth. Methods : Five dogs were fed and 3 were not fed 1.5 g of the inhibitor with meals for 9 weeks. Postprandial and cholecystokinin octapeptide stimulated pancreatic secretion, and fecal balance studies were performed at intervals. After the experiment, the pancreas was analyzed. Results: Weight loss was similar in both groups. Amylase inhibition persisted throughout the 9 weeks; it declined from 91% to 37% from the first to the sixth postprandial hour. Amylase inhibition decreased plasma glucose levels during the first hour ( P < 0.05), increased carbohydrate delivery to the ileum (315 vs. 555 mg/h; P = 0.002), and increased cholecystokinin octapeptide-stimulated amylase secretion. However, amylase inhibition did not significantly change plasma concentrations of insulin, peptide YY or neurotensin, postprandial pancreatic secretion, gastrointestinal transit or pancreatic weight, and protein or DNA content. Conclusions : Prandial ingestion of 1.5 g of the inhibitor for 9 weeks reduces postprandial amylase levels enough to delay carbohydrate digestion and absorption and lower plasma glucose levels without altering pancreatic growth. This dose may be effective to treat diabetes mellitus but not obesity.

Aspirin inhibits secretagogue-stimulated and postprandial pancreatic exocrine secretion in conscious rats.

The effect of salicylate and nonsalicylate antiinflammatory drugs and prostaglandins (PGs) on pancreatic exocrine secretion are controversial. We studied the effect of aspirin (ASA) on secretin- and cholecystokinin (CCK)- or meal-stimulated pancreatic secretion. The interrelation between ASA, PG, and pancreatic exocrine secretion was also investigated. Conscious rats with chronic duodenal, pancreatic, and biliary cannulas received secretin (5 pmol/kg/h, i.v.) and CCK (56 pmol/kg/h) or a meal with administration of cimetidine (20 mg/kg/h, i.v.), ASA (1.2, 12, or 60 mumol/h, i.v.), Salicylic acid (SA) (1.2, 12, or 60 mumol/h, i.v.), prostaglandin E2 (PGE2) (10 micrograms/kg/h), or indomethacin (2 mg/kg) was given, respectively. Pancreatic flow volume, bicarbonate, and protein were determined every 15 min. An inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) (36 micrograms/kg/h) and an activator, phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate, TPA) (100 ng/kg/h) were used for evaluation of the role of protein kinase C on basal and secretagogue-stimulated pancreatic secretion. ASA, but not SA inhibited the secretin- and CCK-stimulated pancreatic secretion including volume, bicarbonate, and protein in a dose-dependent manner without affecting basal pancreatic secretion. ASA and indomethacin suppressed meal-stimulated pancreatic secretion up to 83.8%. PGE2 significantly inhibited the secretin- and CCK-stimulated pancreatic secretion which was further suppressed by the concomitant ASA infusion. Modulation of protein kinase C failed to affect pancreatic secretion. The data indicate that ASA inhibits both secretin- and CCK-stimulated pancreatic secretion by a mechanism independent of prostaglandin biosynthesis inhibition.