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Quarterly Journal of Experimental... Jul 1986Pancreatic function was measured in four ewes following vagal stimulation under control conditions and after the induction of alloxan diabetes. The volume and protein...
Pancreatic function was measured in four ewes following vagal stimulation under control conditions and after the induction of alloxan diabetes. The volume and protein content of the pancreatic juice was measured along with simultaneous measurement of blood glucose and plasma insulin. The volume of pancreatic juice and its protein content decreased markedly in the diabetic state and returned to the initial value after insulin treatment. In normal animals, vagal stimulation markedly increased; the volume of pancreatic secretion and its protein content as well as the plasma insulin concentration. In the diabetic animals vagal stimulation caused only a slight increase in the protein content of pancreatic juice and plasma insulin concentration. It is suggested that insulin is probably one of the more important factors directly regulating the secretion of pancreatic juice.
Topics: Animals; Diabetes Mellitus, Experimental; Electric Stimulation; Female; Insulin; Pancreatic Juice; Parasympathetic Nervous System; Proteins; Sheep; Vagus Nerve
PubMed: 3532163
DOI: 10.1113/expphysiol.1986.sp002998 -
American Journal of Physiology.... Oct 2012The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings....
The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings. Pancreatic function studies in humans have been done by sampling the jejunal fluid. However, it has been difficult to separately study the function of pancreatic and biliary systems in humans with CF, because jejunal fluid contains a mixture of bile and pancreatic fluids. In contrast, pancreatic and biliary ducts open separately into the porcine intestine; therefore, biliary and pancreatic fluid can be individually analyzed in CF pigs. We studied newborn wild-type (WT) and CF pigs and found that CFTR was localized to the pancreatic ducts. We collected bile and pancreatic fluid and analyzed pancreatic enzymes with activity assays and immunoblot. Pancreatic enzyme expression was significantly decreased in CF compared with WT pigs. The volume and pH of pancreatic fluid were significantly lower and protein concentration was >5-fold higher in CF pigs. Secretin stimulation increased pancreatic fluid volume and pH in WT, but not CF, pigs. Baseline bile volume did not differ between WT and CF pigs, but volume did not increase in response to secretin in CF pigs. Bile pH was lower and protein concentration was twofold higher in CF pigs. These results indicate that pancreatic and biliary secretions are altered in CF pigs. Abnormal pancreatic and biliary secretion in CF may have important implications in disease pathogenesis.
Topics: Amylases; Animals; Bile Ducts; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Pancreas; Pancreatic Juice; Swine; Trypsin
PubMed: 22936270
DOI: 10.1152/ajpgi.00030.2012 -
Asian Journal of Surgery Feb 2019Octreotide is known to decrease the rate of postoperative complication after pancreatic resection by diminishing exocrine function of the pancreas. The aim of this study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Octreotide is known to decrease the rate of postoperative complication after pancreatic resection by diminishing exocrine function of the pancreas. The aim of this study was to evaluate the effect of octreotide in decreasing exocrine excretion of pancreas and preventing pancreatic fistula.
MATERIALS AND METHODS
Prospective randomized trial was conducted involving 59 patients undergoing pancreaticoduodenectomy for either malignant or benign tumor, 29 patients were randomized to receive octreotide; 30 patients allotted to placebo. All pancreaticojejunal anastomosis was performed with external stent of negative-pressured drainage and the amount of pancreatic juice through the external stent was measured until postoperative 7th day. Pancreatic fistula was recorded.
RESULTS
There were no differences in demographics, pancreatic texture and pancreatic duct diameter between the octreotide and placebo group. The median output of pancreatic juice was not significantly different between both groups during 7 days after surgery. When the patients were stratified according to the diameter of pancreatic duct (duct ≤5 mm, > 5 mm), there were no significant differences in daily amount of pancreatic juice, however, when stratified according to pancreatic texture, median output of pancreatic juice was significantly lower in patients with hard pancreas compared with those with soft pancreas from 5 day to 7 day after surgery (p < 0.05). No significant differences in pancreatic fistula and postoperative complications were found between the octreotide and placebo groups.
CONCLUSIONS
Prophylactic octreotide is not effective to inhibit the exocrine secretion of the remnant pancreas and does not decrease the incidence of pancreatic fistula after pancreaticoduodenectomy.
Topics: Aged; Aged, 80 and over; Biomarkers; Drug Administration Schedule; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Male; Middle Aged; Octreotide; Pancreas, Exocrine; Pancreatic Fistula; Pancreatic Juice; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications; Prospective Studies; Treatment Outcome
PubMed: 30262436
DOI: 10.1016/j.asjsur.2018.08.006 -
American Journal of Physiology.... May 2001We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with...
We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.
Topics: Animals; Antibodies; Duodenum; Enkephalin, Methionine; Hydrochloric Acid; Infusions, Intravenous; Infusions, Parenteral; Kinetics; Male; Naloxone; Pancreas; Pancreatic Juice; Perfusion; Rats; Rats, Sprague-Dawley; Secretin; Somatostatin
PubMed: 11292597
DOI: 10.1152/ajpgi.2001.280.5.G890 -
Poultry Science Jul 1978The relationship between the intestinal movements and the pancreatic juice secretion in the domestic chicken was studied. The main pancreatic ducts of commercial...
The relationship between the intestinal movements and the pancreatic juice secretion in the domestic chicken was studied. The main pancreatic ducts of commercial broiler-type chickens 12 to 14 weeks of age were cannulated, and the pancreatic secretions were recorded by a drop counter. Balloon catheters for monitoring the intestinal movements were implanted in the proximal duodena in the same animals. Feeding and drinking activities were monitored by photocells. The recordings from the drop counter, the balloon catheter, and the feeding and drinking activity monitor were made in relation to the time of day. These recordings indicated that the pancreatic secretory rate correlates with the pattern of intestinal movements of the proximal duodenum in the domestic chicken. The data also suggest the movement of chyme in the duodenum under ad libitum feeding conditions to be at a steady state during the light period. During the dark period, the intestinal movements and the flow of pancreatic juice are intermittent.
Topics: Animals; Chickens; Gastrointestinal Motility; Light; Pancreatic Juice
PubMed: 674068
DOI: 10.3382/ps.0571084 -
Cancer Medicine Aug 2019Intraductal papillary mucinous neoplasm (IPMN) of pancreas has a high risk to develop into invasive cancer or co-occur with malignant lesion. Therefore, it is important...
Intraductal papillary mucinous neoplasm (IPMN) of pancreas has a high risk to develop into invasive cancer or co-occur with malignant lesion. Therefore, it is important to assess its malignant risk by less-invasive approach. Pancreatic juice cell-free DNA (PJD) would be an ideal material in this purpose, but genetic biomarkers for predicting malignant risk from PJD are not yet established. We here performed deep exome sequencing analysis of PJD from 39 IPMN patients with or without malignant lesion. Somatic alterations and copy number alterations (CNAs) detected in PJD were compared with the histologic grade of IPMN to evaluate their potential as a malignancy marker. Somatic mutations of KRAS, GNAS, TP53, and RNF43 were commonly detected in PJD of IPMNs, but no association with the histologic grades of IPMN was found. Instead, mutation burden was positively correlated with the histologic grade (r = 0.427, P = 0.015). We also observed frequent copy number deletions in 17p13 (TP53) and amplifications in 7q21 and 8q24 (MYC) in PJDs. The amplifications in 7q21 and 8q24 were positively correlated with the histologic grade and most prevalent in the cases of invasive carcinoma (P = 0.002 and 7/11; P = 0.011 and 6/11, respectively). We concluded that mutation burden and CNAs detected in PJD may have potential to assess the malignant progression risk of IPMNs.
Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; DNA Copy Number Variations; Disease Progression; Female; Gene Regulatory Networks; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Neoplasm Grading; Pancreatic Juice; Pancreatic Neoplasms; Exome Sequencing
PubMed: 31225717
DOI: 10.1002/cam4.2340 -
Nature Communications Mar 2016Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils...
Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts.
Topics: Animals; Ceruletide; Chromatin; Cytokines; Disease Models, Animal; Extracellular Traps; Flow Cytometry; Humans; Hydrolases; Immunohistochemistry; Interleukin-17; Mice; Neutrophils; Pancreas; Pancreatic Ducts; Pancreatic Juice; Pancreatitis; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 26964500
DOI: 10.1038/ncomms10973 -
Gut Jun 1970Pancreatic exocrine function tests and plasma insulin curves after a glucose load have been performed in 74 patients, 32 with no significant pancreatic disease, 31 with...
Pancreatic exocrine function tests and plasma insulin curves after a glucose load have been performed in 74 patients, 32 with no significant pancreatic disease, 31 with various disorders of the pancreas, and 11 with postmature diabetes mellitus. Exocrine function was impaired in all patients with chronic pancreatitis and chronic relapsing pancreatitis, whereas insulin production was defective in seven of 10 of those with chronic pancreatitis, and in one of seven with chronic relapsing pancreatitis. The findings in other examples of pancreatic disease are mentioned. Two out of four patients presenting with diabetes mellitus, who were found to have a flat plasma insulin curve, proved on investigation to have chronic pancreatitis. The results of plasma insulin response curves in this series are discussed in relation to pancreatic disease and their possible value in diagnosis.
Topics: Adolescent; Adult; Aged; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatic Diseases; Pancreatic Juice; Pancreatitis
PubMed: 5430381
DOI: 10.1136/gut.11.6.524 -
Molecular Cancer Jun 2010Pancreatic intraepithelial neoplasias (PanINs) are precursors of malignant pancreatic cancer, an ideal stage for early cancer detection. We applied quantitative...
BACKGROUND
Pancreatic intraepithelial neoplasias (PanINs) are precursors of malignant pancreatic cancer, an ideal stage for early cancer detection. We applied quantitative proteomics to identify aberrantly elevated proteins in pancreatic juice samples derived from patients with PanIN3.
RESULTS
Twenty proteins were found elevated in all three PanIN juices by at least two-fold. Among these proteins, anterior gradient-2 (AGR2) was found to be 2-10 fold elevated in PanIN3 juice samples analyzed by quantitative proteomics. An ELISA assay was developed to evaluate AGR2 levels in 51 pancreatic juice samples and 23 serum samples from patients with pancreatic cancer, pre-malignant lesions (including PanIN3, PanIN2, Intraductal Papillary Mucinous Neoplasms (IPMNs)) and benign disease controls (including chronic pancreatitis). AGR2 levels in the pancreatic juice samples were found significantly elevated in patients with pre-malignant conditions (PanINs and IPMNs) as well as pancreatic cancer compared to control samples (p < or = 0.03). By ROC analysis, the AGR2 ELISA achieved 67% sensitivity at 90% specificity in predicting PanIN3 juice samples from the benign disease controls.
CONCLUSIONS
These results suggest that elevation of AGR2 levels in pancreatic juice occurs in early pancreatic cancer progression and could be further investigated as a potential candidate juice biomarker for early detection of pancreatic cancer.
Topics: Adolescent; Adult; Aged; Area Under Curve; Biomarkers, Tumor; Blotting, Western; Carcinoma in Situ; Early Detection of Cancer; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Immunoprecipitation; Male; Middle Aged; Mucoproteins; Oncogene Proteins; Pancreatic Juice; Pancreatic Neoplasms; Precancerous Conditions; Proteins; Proteomics; ROC Curve; Young Adult
PubMed: 20550709
DOI: 10.1186/1476-4598-9-149 -
The Journal of Physiology Mar 19751. The orgin of the calcium secreted by the pancreas has been investigated in vivo in the guinea-pig by a study carried out in parallel (a) in the juice secreted in...
1. The orgin of the calcium secreted by the pancreas has been investigated in vivo in the guinea-pig by a study carried out in parallel (a) in the juice secreted in response to the injection of either secretin or caerulein and (b) in the pancreatic tissue and in cell fractions isolated thereform. 2. In agreement with previous findings we observed that the concentration of calcium is low in the secretin-stimulated and high in the caerulein-stimulated juice. In the latter calcium and protein are proportional (cal0 n-mole:mg). 3. After I.V. injection of 45Ca the radioactivity decreases rapidly and quasi-exponentially in the blood plasma. A roughly parallel time course is found in the secretin-stimulated juice: the evolution of the juice: plasma radioactivity ratio resembles that observed with the extraceullar space marker [3H]D-sorbitol. In contrast, the time course of 45Ca in plasma and caerulein-stimulated juice are not proportional: the high levels characteristic of this juice are reached several minutes after the injection and maintained thereafter. This increase is followed ca. 50 min later by the appearance of the newly synthesized [3H]L-leucine-labelled proteins. 4. The pancreatic tissue is rich in calcium which is localized primarily in zymogen granules (Ca.36 n-mole:mg protein) and mitochondria; the soluble cytoplasm is low in calcium. 5. The injected 45Ca accumulates in zymogen granules faster than [3H]L-leucine-labelled proteins. The 45Ca:protein ratio of these organelles is considerably lower than that of the caerulein-stimulated juice. 6. It is concluded (a) that calcium is secreted in to the pancreatic juice in two fractions, one (possibly released by simple diffusion) associated with the electrolyte component, the other with protein of the juice, (b) that zymogen granules are the major, but not the only source of the latter fraction, and (c) that the zymogen granule-associated calcium joins the exportable proteins some time after their synthesis, possibly in the Golgi complex and/or in the condensing vacuoles.
Topics: Animals; Calcium; Ceruletide; Cytoplasm; Guinea Pigs; Leucine; Microsomes; Mitochondria; Pancreas; Pancreatic Juice; Proteins; Secretin; Sorbitol; Subcellular Fractions
PubMed: 1142221
DOI: 10.1113/jphysiol.1975.sp010865