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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose intolerance is often associated with pancreatitis. Pancreatitis-induced diabetes represents a different clinical syndrome than type I and type II diabetes mellitus. Patients with pancreatitis-induced diabetes may be extremely sensitive to exogenous insulin, rarely develop ketoacidosis, and rarely exhibit classic diabetic complications, such as retinopathy, nephropathy, or accelerated vasculopathy. Pancreatic polypeptide (PP) deficiency has been implicated in the defect of glucose homeostasis found after pancreatitis. This study evaluated intravenous and oral glucose tolerance and insulin response to glucose loading, in the setting of pancreatitis, with and without short-term PP replacement. Dogs (n = 7) underwent pancreatic duct ligation (PDL) and were studied with and without PP infusion (2 micrograms/kg/hr) before PDL and at 1 week, 6 weeks, and 4 months after PDL by means of intravenous and oral glucose tolerance tests. Basal and bombesin-stimulated PP levels at 4 months after PDL were subnormal, verifying PP deficiency in these animals with pancreatitis. PP levels during PP infusion reproduced normal postcibal levels, averaging 897 +/- 40 pg/ml. Glucose tolerance, expressed as the glucose decay constant for the intravenous glucose tolerance tests and as the integrated glucose response for the oral glucose tolerance tests, deteriorated over time and was not improved by acute PP replacement. The integrated insulin response to glucose was not affected by PP. The acute infusion of PP at a dose that reproduces normal postprandial PP levels fails to improve glucose tolerance or augment insulin release in this model of pancreatitis-induced diabetes.
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PMID:The effect of pancreatic polypeptide infusion on glucose tolerance and insulin response in longitudinally studied pancreatitis-induced diabetes. 219 57

Findings of dynamic cholangiomanometry with the analysis of the tension curves are overviewed. This technique helped reveal different functional ailments of the bile papilla in major variants of the cholelithiasis course (acute obstructive++ cholecystitis, recurrent pancreatitis, and choledocholythiasis with obstructive jaundice). Parallel radioimmunoassay-based studies of a series of gastrointestinal polypeptides (insulin, glucagon, gastrin, vasoactive peptide, bombesin , and somatostatin) were conducted to determine the importance of these polypeptides in the pathogenesis of cholelithiasis complications. The levels of certain polypeptides were found to be related to the clinical manifestations of the disease. The complex assessment of the bile papilla function and gastrointestinal polypeptide concentrations offers a possibility for elaborating the pathogenetically relevant methods of therapy for this group of diseases.
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PMID:[Plasma levels of various gastrointestinal polypeptides in patients with cholelithiasis and different degree of functional disorders of the major duodenal papilla]. 227 84

Supramaximal stimulation of the rat pancreas in vivo with caerulein elicits a sharp decline in pancreatic juice volume and protein outputs and initiates acute edematous pancreatitis within 30 min. Because of the similar effects of caerulein and bombesin on pancreatic exocrine function, we examined in unconscious rats (a) the effects of a continuous, 4-h intravenous infusion of varying doses (0.2-40.0 nmol/kg/h) of bombesin on pancreatic juice volume and protein output, and (b) whether supramaximal doses of bombesin produce acute edematous pancreatitis. A maximal, fivefold and 17-fold rise in pancreatic juice volume and protein output was achieved with intravenous doses of 1.0 and 4.0 nmol of bombesin/kg/h, respectively. Pancreas weights in rats infused with bombesin as high as 40.0 nmol/kg/h were not significantly different from control animal values (no bombesin infusion) and serum amylase concentrations were only moderately (twofold) elevated over control values in rats i.v. infused with 4.0-40.0 nmol of bombesin/kg/h. The pancreas in rats treated with the highest dose of bombesin (40.0 nmol/kg/h) revealed sparsely scattered microvacuoles in a few acinar cells and minor evidence of interacinar edema. It is concluded that supramaximal stimulation of the rat pancreas in vivo with bombesin fails to elicit acute edematous pancreatitis and appears to be related to the ability of bombesin, in contrast to supramaximal doses of caerulein, to continuously stimulate maximal pancreatic juice secretion.
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PMID:Pancreatic exocrine function in unconscious rats treated with submaximal, maximal, and supramaximal doses of bombesin tetradecapeptide. 271 5

Cholecystokinin and its analogues such as cerulein, muscarinic cholinergic agonists, and gastrin-releasing peptide (bombesin) bind to distinct receptors on the surface of pancreatic acinar cells and stimulate digestive protein secretion by a calcium-dependent mechanism. The mechanisms of the calcium-dependent secretagogue classes has been assumed to be similar. In this study we have noted that dispersed pancreatic acini secrete comparable maximal rates of amylase in response to cerulein and bombesin; however, the maximal level of phosphatidylinositol 4,5-bisphosphate hydrolysis was less with bombesin than with cerulein. The high agonist dose-inhibited secretion in vitro observed with cerulein was absent with bombesin. In vivo administration of supramaximal secretory stimulating doses of both cerulein and bombesin caused pancreatic edema; however, the increase in serum concentrations of amylase and lipase induced by cerulein treatment was not detected with bombesin. These data indicate that cerulein and bombesin display distinctly different effects on the exocrine pancreas both in vivo and in vitro. That pancreatic edema and elevated serum enzyme levels may be the result of different cellular mechanisms in experimental pancreatitis is strongly suggested.
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PMID:Different effects of hyperstimulation by similar classes of secretagogues on the exocrine pancreas. 767 26

The innervation of the sphincter of Oddi (SO) has been extensively studied experimentally, but human studies have not been published, which is why this study was undertaken. Biopsies, taken by gastroscopy-biopsy forceps from duodenal epithelium of the papilla of Vater and from ampullary epithelium after sphincterotomy, did not demonstrate nerves and could not be used for studying SO innervation. Therefore SO specimens were obtained from brain-dead organ donors (N = 5) and from autopsies (N = 14). By staining with a myelin marker S-100, a rich network of nerves was demonstrated in SO. The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI) (or its immunologically similar human equivalent peptide histidine methioninamide, PHM), neuropeptide Y, calcitonin gene-related peptide (CGRP), galanin, substance P, enkephalin, bombesin, and somatostatin were studied by immunohistochemical technique. SO demonstrated immunoreactivity for VIP, PHI (PHM), neuropeptide Y, CGRP, galanin, somatostatin, substance P, and enkephalin, but no immunoreactivity was observed for bombesin. The SO immunoreactivity was similar in specimens from organ donors and from autopsies of victims of violence without pancreatobiliary diseases (N = 3) when the specimens were taken within 48 hr of death. Autopsy specimens of SO from subjects with gallstone disease (N = 5), recurrent pancreatitis (N = 3) or periampullary carcinoma (N = 3) also demonstrated similar immunoreactivity. We conclude that VIP-, PHI- (PHM-), neuropeptide Y-, CGRP-, galanin-, substance P-, somatostatin-, and enkephalin-like immunoreactivity occur in human SO. These neuropeptides may have role in the neural control of human SO function.
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PMID:Peptidergic innervation of human sphincter of Oddi. 831 11

We compared the cellular events induced by hyperstimulation of rats with caerulein which induces acute pancreatitis, to bombesin, which does not induce pancreatitis. Both secretogogues induced the intracellular activation of trypsinogen and the colocalization of lysosomal hydrolases and zymogen granules within 10-15 minutes. These data indicate that these parameters, previously thought to be crucial initiating events of pancreatitis, are not definitive cellular markers of the disease. We then compared the abilities of the two secretagogues to activate stress-activated protein kinase (SAPK). Significant effects of caerulein hyperstimulation on SAPK activity were observed within 5 minutes, the maximum (57-fold) activation was evident after 15 minutes, and levels remained above control for at least 3 hours. In comparison, hyperstimulation with bombesin induced a maximal 5-fold increase of SAPK activity which returned to basal within one hour. These data indicate that SAPK activity is the earliest and best correlated cellular marker associated with secretagogue-induced pancreatitis.
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PMID:Stress-activated protein kinase activation is the earliest direct correlate to the induction of secretagogue-induced pancreatitis in rats. 885 94

The pathological activation of digestive zymogens within the pancreatic acinar cell probably plays a central role in initiating many forms of pancreatitis. To examine the relationship between zymogen activation and acinar cell injury, we investigated the effects of secretagogue treatment on isolated pancreatic acini. Immunofluorescence studies using antibodies to the trypsinogen-activation peptide demonstrated that both CCK (10(-7) M) hyperstimulation and bombesin (10(-5) M) stimulation of isolated acini resulted in trypsinogen processing to trypsin. These treatments also induced the proteolytic processing of procarboxypeptidase A1 to carboxypeptidase A1 (CA1). After CCK hyperstimulation, most CA1 remained in the acinar cell. In contrast, the CA1 generated by bombesin was released from the acinar cell. CCK hyperstimulation of acini was associated with cellular injury, whereas bombesin treatment did not induce injury. These studies suggest that 1) proteolytic zymogen processing occurs within the pancreatic acinar cell and 2) both zymogen activation and the retention of enzymes within the acinar cell may be required to induce injury.
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PMID:Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury. 981 31

Positive signs of pancreas regeneration were observed in rats after induced pancreatitis and partial pancreatectomy (1,2). Although the human pancreas did not regenerate after partial anatomic resection (3), the pig pancreas exhibited growth responses to bombesin after partial pancreatectomy (4). This study was undertaken to establish the time course of pancreatic inflammation, apoptosis, and hypertrophy and/or hyperplasia after partial pancreatectomy in pigs.
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PMID:Pancreatic inflammation, apoptosis, and growth: sequential events after partial pancreatectomy in pigs. 1103 78

Acute pancreatitis is an auto-digestive disease resulting in inflammation. At the cellular level, acute pancreatitis disrupts posttranslational protein processing and traffic in the secretory pathway, and zymogens become activated in the acinar cell. To better understand the disruption of the secretory pathway in pancreatitis, pulse-chase [(35)S]met/cys analysis was used to study the effects of supramaximal cerulein stimulation on posttranslational modification in the secretory pathway of the major sulfated glycoprotein of the mouse pancreas, pro-Muclin, and the lysosomal membrane protein LAMP1. Maximal cerulein or high concentration bombesin stimulation had little effect on glycoprotein processing. By contrast, supramaximal cerulein stimulation strongly inhibited pro-Muclin processing as measured by the failure of Muclin to attain its normal mature size of 300 kDa and to become highly sulfated and decreased proteolytic cleavage of pro-Muclin to produce apactin. Digestion of immunoprecipitated [35S]met/cys-labeled Muclin and LAMP1 with endoglycosidase H demonstrated that the supramaximal cerulein-induced block in processing occurred before the medial Golgi compartment. With supramaximal cerulein stimulation, vacuoles formed which contained Muclin, amylase, and LAMP1. Earlier autoradiographic studies showed that newly synthesized proteins end up in pancreatitis-associated vacuoles, so it is likely that glycoproteins with incomplete posttranslational processing are also present in vacuoles. Because glycoproteins are believed to protect the membranes of lysosomes and zymogen granules, when they are not correctly processed, their defensive mechanisms may be impaired, and this could contribute to vacuole fragility in pancreatitis.
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PMID:Altered posttranslational processing of glycoproteins in cerulein-induced pancreatitis. 1586 54

To examine mechanisms that might be related to biliary pancreatitis, we examined the effects of pancreatic duct ligation (PDL) with pancreatic stimulation in vivo. PDL alone caused no increase in pancreatic levels of trypsinogen activation peptide (TAP), trypsin, or chymotrypsin and did not initiate pancreatitis. Although bombesin caused zymogen activation within the pancreas, the increases were slight and it did not cause pancreatitis. However, the combination of PDL with bombesin resulted in prominent increases in pancreatic TAP, trypsin, chymotrypsin, and the appearance of TAP in acinar cells and caused pancreatitis. Disruption of the apical actin network in the acinar cell was observed when PDL was combined with bombesin but not with PDL or bombesin alone. These studies suggest that when PDL is combined with pancreatic acinar cell stimulation, it can promote zymogen activation, the retention of active enzymes in acinar cells, and the development of acute pancreatitis.
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PMID:Effects of pancreatic duct ligation on pancreatic response to bombesin. 1629 54


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