Age-associated changes in pancreatic exocrine secretion of the isolated perfused rat pancreas / 한국실험동물학회지

Gut functions, such as gastrointestinal motility, gastric secretion and pancreatic secretion, were reduced with age. Glucose tolerance is impaired, and the release of insulin and beta-cell's sensitivity on glucose are reduced with age. However, a lot of controversial data have been reported as insulin concentrations after glucose ingestion are either higher or no different in elderly and young subjects. Thus, this study was aimed to investigate whether aging could affect pancreatic exocrine secretion and its action mechanisms. An isolated perfused rat pancreatic model was used to exclude the effects of external nerves or hormones. Pancreatic secretion was increased by CCK under 5.6 mM glucose background in the isolated perfused pancreas of young (3 months), 12 months and 18 months aged rats. There was no significant difference between young and aged rats. In 3 months old rats, CCK-stimulated pancreatic secretion was potentiated under 18 mM glucose background. However, the potentiation effects of endogenous insulin and CCK were not observed in 12 and 18 months old rats. Exogenous insulin also potentiated CCK-stimulated pancreatic secretion in 3 months old rats. Similarly, exogenous insulin failed to potentiate CCK-stimulated pancreatic secretion as that of 3 months old rats. Wet weight of pancreas and amylase content in pancreatic tissue were not changed with age. These results indicate that pancreatic exocrine secretion is reduced with age and endogenous insulin secretion and/or action is involved in this phenomenon.

Effect of early enteral nutrition on pancreatic exocrine secretion in dogs with acute necrotizing pancreatitis / 中华胰腺病杂志

Objective To evaluate the effect of early enteral nutrition (EN) on the pancreatic exocrine secretion in dogs with acute necrotizing panereatitis (ANP). Methods ANP model was induced by injection of mixtured solution of 5% sodium tanrecholate and trypsin into the pancreatic duct. Thirty dogs were randomly divided into total parenteral nutrition (TPN) group (n=5), duodenal PEPTI-2000VARIENT (DP) group (n=5), duodenal Nutrison MuhiFibre (DN) group (n=5), jejunal PEPTI-2000VARIENT (JP) group (n=5), jejunal Nutrison MuhiFibre (JN) group (n=5). The dogs were treated by either TPN or EN 24 hours after ANP model induction and the nutrition support lasted for 5 days. Serum amylase, LDH, lipase, secretin (SEC), cholecystokinin (CCK) and gastrin were measured at 1, 2, 3, 4, 5 d. Pancreatic juice was collected for 3 hours after TPN or EN started, and the amount of pancreatic juice and levels of proteinase, amylase, lipase, HCO3-, K+, Cl-, Na+ were determined. Dogs in each group were sacrificed at day 7. Histological and ultra-structure changes of the pancreatic tissues were evaluated pathologically. Results The levels of serum amylase, LDH, lipase, CCK, amount of pancreatic secretion and K+, Cl+, Na+ were not significantly different among these groups. The levels of plasma SEC and gastrin, HCO3-, proteinase, amylase, lipase in the duodenal nutrition groups were significantly higher than those in TPN group (P<0.05). The above mentioned parameters in the jejunal nutrition group were significantly lower than those in the duodenal group (P<0.05) and higher than those in the TPN group without significant difference. Among the 2 jejunal nutrition groups, the levels of plasma gastrin, HCO3- in pancreatic juice, proteinase, amylase, lipase in the JP group were significantly higher than those in the JN group (P<0.05). The above mentioned parameters in the DP group were significantly lower than those in the DN group (P<0.05). The amount of pancreatic secretion, HCO3-,K+, Cl+, Na+ were not significantly different among these groups. The pathological changes were similar among these groups, and the extent of pathological changes was relatively better in the JP group. The amount and density of intracytoplasm zymogen granules of pancreatic acinar cell were not significantly lower than those in the TPN group. Conclusions The delivery of nutrients to the proximal jejunum with elemental low-fat diets did not increase the pancreatic exacrine activity.

Effects of gamma-Aminobutyric Acid on Intrinsic Cholinergic Action in Exocrine Secretion of Isolated, Perfused Rat Pancreas

gamma-Aminobutyric acid (GABA) has been reported to enhance exocrine secretion evoked not only by secretagogues but also by intrinsic neuronal excitation in the pancreas. The pancreas contains cholinergic neurons abundantly that exert a stimulatory role in exocrine secretion. This study was undertaken to examine effects of GABA on an action of cholinergic neurons in exocrine secretion of the pancreas. Intrinsic neurons were excited by electrical field stimulation (EFS; 15 V, 2 msec, 8 Hz, 45 min) in the isolated, perfused rat pancreas. Tetrodotoxin or atropine was used to block neuronal or cholinergic action. Acetylcholine was infused to mimic cholinergic excitation. GABA (30microM) and muscimol (10microM), given intra-arterially, did not change spontaneous secretion but enhanced cholecystokinin (CCK; 10 pM) -induced secretions of fluid and amylase. GABA (3, 10, 30microM) further elevated EFS-evoked secretions of fluid and amylase dose-dependently. GABA (10, 30, 100microM) also further increased acetylcholine (5microM) -induced secretions of fluid and amylase in a dose-dependent manner. Bicuculline (10microM) effectively blocked the enhancing effects of GABA (30microM) on the pancreatic secretions evoked by either EFS or CCK. Both atropine (2microM) and tetrodotoxin (1microM) markedly reduced the GABA (10microM) -enhanced EFS- or CCK-induced pancreatic secretions. The results indicate that GABA enhances intrinsic cholinergic neuronal action on exocrine secretion via the GABAA receptors in the rat pancreas.

Effects of gamma-Aminobutyric Acid on Pancreatic Amylase Secretion Evoked by Sodium Oleate in Anesthetized Rats

gamma-Aminobutyric Acid (GABA) is contained in pancreatic islet beta-cells although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA (10, 30 and 100micromol/kg/h), given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA (30micromol/kg/h) also further increased the amylase secretion stimulated by CCK+(30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA (10, 30 and 100micromol/kg/h) also dose-dependently elevated pancreatic amylase secretion evoked by CCK+alone. Bicuculline (100micromol/kg/h), a GABAA-receptor antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK+plus secretin or CCK+alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via GABAA-receptors in anesthetized rats, which may account for elevating the action of CCK+released by sodium oleate.

Regulatory Effects of Nitric Oxide (NO) on Pancreatic Exocrine Secretion / 대한해부학회지

Recently nitric oxide (NO) is known as a bioactive molecule modulating secretory activity in various glandular tissues. Previously we have localized bNOS, a neuronal isoform of nitric oxide synthase, in the pancreatic tissue, particularly in the pancreatic islet of Langerhans and in the neurons of intrapancreatic ganglia. It implies that NO may play the important roles in regulation of pancreatic secretion by transmitting the neuronal signals from autonomic nervous system to endocrine and/or exocrine system of pancreas. We also revealed that NO is involved in regulation of insulin secretion and its synthesis. The present study was designed to elucidate the regulatory effect of NO on the pancreatic exocrine secretion by way of insulo-acinar axis. For the experiment, we observed modification of amylase secretion in the rats treated with N(G)-nitro-L-arginine-methyl ester (NAME), a potent NOS inhibitor. In addition, we observed the expression of clusterin which is known to be a protein associated with cell viability in order to assess the cytotoxic effect of NO. The present study showed that the intra-pancreatic NO is involved in regulation of amylase secretion of pancreatic acinar cells. Amylase immunoreactivity was significantly decreased at 60 and 90 min after NAME injection, although little change was seen during 30 min after treatment. However, the amylase immunoreaction was recovered toward the normal range at 120 min after NAME treatment. In electron-immunolabeling experiment, we observed the secretory granules with higher electron density, but less immunolabeling for amylase at 60~90 min after NAME treatment, while they restored normal feature and labeling density at 120 min. Clusterin expression increased along with the time course of experiment and demonstrated a highest level at 120 min after NAME injection. Taken together, the above results indicate that lowered level of NO induced by NAME treatment reduces amylase secretion of acinar tissue. It implies that increased level of NO in physiological range may stimulate pancreatic exocrine secretion.

Distribution, content and molecular heterogeneity of gastrin-releasing peptide in rat pancreas

Although importance of intrapancreatic neurons containing gastrin-releasing peptide (GRP) in control of exocrine secretion has been raised, the nature of GRP in the pancreas is unclear Thus, the present study was undertaken to see distribution, content and molecular heterogeneity of immunoreactive GRP in the rat pancreas Content of immunoreactive GRP in the rat pancreas was 2 99 +/- 0.66 ng/g wet tissues determined by radioimmunoassay. Immunoreactive GRP was most abundantly expressed in the duodenal part among 3 parts of the pancreas, duodenal, body and splenic part. Vagotomy failed to change the content of immunoreactive GRP in the pancreas. Three distinct forms of immunoreactive GRP, very identical to GRP-27, bombesin-24 and neuromedin C, were observed in the rat pancreas by using reversed phase C18 HPLC and Sephadex G-50 superfine column chromatography. Cell bodies of neurons containing immunoreactive GRP were scattered in pancreatic connective tissues and their nerve fibers innerv ated pancreatic acini and large ducts as determined by immunohistochemistry. The present results suggest that three distinct forms of GRP exist in intrapancreatic GRPergic neurons, which exert a stimulatory role in pancreatic exocrine secretion in rats.

Further characterization of bombesin like immunoreactivities from the skin of Korean fire-bellied toad, Bombina orientalis

Previously, we have isolated authentic bombesin and another bombesin like peptide named bombesin like immunoreactivity (BLI)-K2 from the skin of Korean fire-bellied toad, Bombina orientalis. In the present study, we have newly purified three heterogeneous forms of BLI named BLI-K3, BLI-K4, and BLI-K5 from side fractions obtained in previous isolation of bombesin like peptide. The BLIs were separated into five peaks on a column of C18 preparative HPLC. Among them, three minor peaks containing BLI-K3, K4, and K5 were purified by means of sequential chromatography on the columns of SP cation exchange HPLC and C18 reverse phase HPLC. The purified BLI-K3 and K4 showed high binding affinity to an anti-bombesin serum (LBE 2G-2) with binding potency of 72 and 95%, respectively, relative to that of bombesin. However, they did not possess any distinctive biological activity of bombesin like peptide. On the contrary, the biological activity of BLI-K5 was similar to that of bombesin but its binding affinity to an anti-bombesin serum was low. The results indicate that three heterogeneous forms of BLI were coexpressed with bombesin and BLI-K2 in the skin of B. orientalis. All forms of the purified BLI in the present study were immunologically active but only BLI-K5 possessed the distinctive biological activity of bombesin like peptide.

Effects of total parenteral nutrition and enteral nutrition on pancreatic exocrine secretion and severe acute pancreatitis / 肠外与肠内营养

This review examines the effects of parenteral nutrition(PN) or enteral nutrition(EN) on pancreatic exocrine secretion and severe acute pancreatitis(SAP). There is no evidence that PN support in SAP affects the underlying disease process,but it may prevent the malnutrition and complications.In recent years,EN is considered to be used in that it preserves gut barrier function.PN,in contrast,may result in mucosal atrophy,bacterial translocation and increased rates of catheter related sepsis.The effects of EN on pancreatic exocrine secretion and natural course of SAP are discussed.The safety and feasibility of EN in SAP have been established. EN may even be superior to PN.Some patients,however,cannot tolerate enteral feeding and PN still has a role.