Exploring the Role of G Protein Expression in Sodium Butyrate-Enhanced Pancreas Development of Dairy Calves: A Proteomic Perspective.

The present study evaluated the effects of sodium butyrate (SB) supplementation on exocrine and endocrine pancreatic development in dairy calves. Fourteen male Holstein calves were alimented with either milk or milk supplemented with SB for 70 days. Pancreases were collected for analysis including staining, immunofluorescence, electron microscopy, qRT-PCR, Western blotting, and proteomics. Results indicated increased development in the SB group with increases in organ size, protein levels, and cell growth. There were also exocrine enhancements manifested as higher enzyme activities and gene expressions along with larger zymogen granules. Endocrine benefits included elevated gene expression, more insulin secretion, and larger islets, indicating a rise in ß-cell proliferation. Proteomics and pathway analyses pinpointed the G protein subunit alpha-15 as a pivotal factor in pancreatic and insulin secretion pathways. Overall, SB supplementation enhances pancreatic development by promoting its exocrine and endocrine functions through G protein regulation in dairy calves.

Integrated microRNA-mRNA analysis reveals a possible molecular mechanism of enteritis susceptibility in Litopenaeus vannamei.

Enteritis is one of the main diseases affecting Pacific whiteleg shrimp (Litopenaeus vannamei) in recent years, and it has resulted in huge losses to the aquaculture industry. Prior to this study, the molecular mechanism underlying enteritis in L. vannamei was unclear, and comprehensive multi-omics analysis had not been conducted. In this study, 1209 differentially expressed genes (DEGs) were identified from the hepatopancreas of L. vannamei with and without enteritis. Kyoto Encyclopedia of Genes and Genomes analysis showed that genes were significantly enriched in immune, metabolic, and endocrine regulatory pathways. Forty-eight significantly different microRNAs (miRNAs) were identified in the miRNA-Seq analysis. Further functional annotation analysis showed that the regulatory pathway of target gene enrichment of differentially expressed miRNAs was consistent with DEGs. Through miRNA-mRNA integration analysis, 47 meaningful miRNA-mRNA pairs were obtained, of which melanogenesis and pancreatic secretion were considered key pathways. Subsequent miRNA-mRNA interaction network analysis revealed that mja-miR-6493-3p, Mja-miR-6494, novel-198, novel-272, novel-261, novel-200, novel-183, novel-184, novel-237, and novel-192 may be key miRNAs involved in the regulation of these two signaling pathways. Finally, the RAS signaling pathway was found to inhibit the translation level of proteins in the hepatopancreas. These results suggest that target gene integration analysis of mRNA-miRNA can reveal the molecular mechanism underlying enteritis in L. vannamei and also provide valuable new insights for resisting enteritis.

Effect of Adropin on Pancreas Exocrine Function in a Rat Model: A Preliminary Study.

The aim was to investigate the potential effect of adropin (ADR) on pancreatic−biliary juice (PBJ) secretion (volume, protein content, trypsin activity) in a rat model. The animals were divided into control and five experimental groups: adropin, CCK-8 (CCK-8 stimulation), capsaicin (capsaicin deactivation of afferents), vagotomy (vagotomy procedure), and vagal stimulation (vagal nerve stimulation). The experiment consisted of four phases, during which vehicle (0.9% NaCl) and three ADR boluses (5, 10, and 20 µg/kg BW) were administered i.v. every 30 min. PBJ samples were collected from each rat at 15 min intervals after boluses. Exogenous ADR failed to affect the pancreatic responses after vagotomy and the capsaicin pretreatment and reduced the PBJ volume, protein outputs, and trypsin activity in the adropin, CCK-8, and vagal stimulation groups in a dose-dependent manner. In all these groups, volume of PBJ was reduced only by the highest dose of ADR (p < 0.001 for adropin group and p < 0.01 for CCK-8 and vagal stimulation groups), and the protein outputs were reduced by the administration of ADR 10 µg/kg BW (adropin and CCK-8 groups, p < 0.01 in both cases) and 20 µg/kg BW (p < 0.001 for adropin and CCK-8 groups, p < 0.01 for vagal stimulation group). The 10 µg/kg BW dose of ADR reduced the trypsin output in the CCK-8 group (p < 0.01), and the highest ADR dose reduced the trypsin output in the CCK-8 (p < 0.001) and vagal stimulation (p < 0.01) groups. In conclusion, adropin in the analyzed doses exhibits the negative feedback pathway. This mechanism seems to participate in the regulation of pancreatic juice secretion via an indirect vagal mechanism.

Association between osteocalcin, a pivotal marker of bone metabolism, and secretory function of islet beta cells and alpha cells in Chinese patients with type 2 diabetes mellitus: an observational study.

BACKGROUND: Several recent studies have found that Osteocalcin (OCN), a multifunctional protein secreted exclusively by osteoblasts, is beneficial to glucose metabolism and type 2 diabetes mellitus (T2DM). However, the effects of OCN on islets function especially islet ɑ cells function in patients with type 2 diabetes mellitus characterized by a bi-hormonal disease are still unclear. The purpose of this cross-sectional study was to investigate the relationship between serum OCN and the secretion of islet ß cells and ɑ cells in Chinese patients with type 2 diabetes mellitus. METHODS: 204 patients with T2DM were enrolled. Blood glucose (FBG, PBG0.5h, PBG1h, PBG2h, PBG3h), insulin (FINS, INS0.5h, INS1h, INS2h, INS3h), C-peptide (FCP, CP0.5h, CP1h, CP2h, CP3h), and glucagon (GLA0, GLA0.5 h, GLA1h, GLA2h, GLA3h) levels were measured on 0 h, 0.5 h, 1 h, 2 h, and 3 h after a 100 g standard bread meal load. Early postprandial secretion function of islet ß cells was calculated as Δcp0.5h = CP0.5-FCP. The patients were divided into low, medium and high groups (T1, T2 and T3) according to tertiles of OCN. Comparison of parameters among three groups was studied. Correlation analysis confirmed the relationship between OCN and pancreatic secretion. Multiple regression analysis showed independent contributors to pancreatic secretion. MAIN RESULTS: FBG, and PBG2h were the lowest while Δcp0.5h was the highest in the highest tertile group (respectively, p < 0.05). INS3h, area under the curve of insulin (AUCins3h) in T3 Group were significantly lower than T1 Group (respectively, p < 0.05). GLA1h in T3 group was lower than T1 group (p < 0.05), and GLA0.5 h in T3 group was lower than T2 and T1 groups (p < 0.05). Correlation analysis showed OCN was inversely correlated with Homeostatic model of insulin resistance (HOMA-IR), INS3h, AUCins3h (p < 0.05), and was still inversely correlated with FCP, GLA0.5 h, GLA1h, area under the curve of glucagon (AUCgla3h) (respectively, p < 0.05) after adjustment for body mass index (BMI) and alanine aminotransferase (ALT). The multiple regression analysis showed that OCN was independent contributor to Δcp0.5h, GLA0.5h and GLA1h (respectively, p < 0.05). CONCLUSIONS: Higher serum OCN level is closely related to better blood glucose control, higher insulin sensitivity, increased early-phase insulin secretion of islet ß cells and appropriate inhibition of postprandial glucagon secretion of islet ɑ cells in adult patients with type 2 diabetes mellitus.

Genomic divergence during artificial selection by feed conversion ratio in Pekin ducks.

Pekin ducks are world-famous for its fast growth and have become the majority of breeds rearing in duck industry. Feed conversion ratio (FCR) is an important trait in Pekin ducks breeding and production, and the underlying biological processes are complex. To gain an insight to the possible biological mechanism underlying the FCR in Pekin ducks, an artificial selection population (S) and a natural population (Z7) were used in this study. The FCR of S line decreased from 2.184 ± 0.057 in the first generation to 1.886 ± 0.063 in the eighth generation, which displays significantly low FCR (p = 0.0032) than that of the Z7 line (2.23 ± 0.046). Then, 9 samples from eighth generation of S line and 10 samples from Z7 were used for whole-genome resequencing. Analyses of FST, θπ and XP-EHH revealed 450, 479 and 356 candidate genes, which involved in 1,955, 1,933 and 1,964 candidate divergent regions (CDRs), respectively. And the integration of three approaches resulted in 30 overlapping genes. Functional analysis of 30 candidate genes revealed that variants of KCNQ1 and ADCY7, which were involved in the pancreatic secretion signal pathway, could be important molecular markers for high feed conversion efficiency in S line breeding.

Critical thresholds: key to unlocking the door to the prevention and specific treatments for acute pancreatitis.

Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are: (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.

Endoscopic ultrasound-based multimodal evaluation of the pancreas in patients with suspected early chronic pancreatitis.

BACKGROUND: Diagnosis of early chronic pancreatitis is a clinical challenge and hindered by the lack of a gold standard. Endoscopic ultrasound (EUS) and the endoscopic pancreatic function test (ePFT) are the most sensitive morphological and functional methods in this setting. EUS-elastography allows for the quantification (strain ratio) of pancreatic fibrosis, and the dynamic evaluation of the main pancreatic duct compliance provides additional information. We developed a multimodal EUS-based approach for the evaluation of the pancreas by integrating these four methods in a single procedure. OBJECTIVE: We aim to describe morphological and functional pancreatic abnormalities in patients with clinical suspicion of chronic pancreatitis and inconclusive EUS findings by using the multimodal EUS-based approach. METHODS: This was a prospective, cross-sectional, observational study of patients with clinically suspected chronic pancreatitis and indeterminate EUS criteria of the disease. EUS criteria of chronic pancreatitis, quantitative pancreatic elastography, ePFT and compliance of the main pancreatic duct were evaluated in a single procedure. RESULTS: In total, 53 patients with 3-4 EUS criteria of chronic pancreatitis were included (mean age 39.7 years, 29 male). Strain ratio was abnormally high in all patients. Peak bicarbonate concentration was decreased in 43 patients (81.1%) and the main pancreatic duct compliance was reduced in 41 patients (77.3%). Some 34 patients (64.1%) had abnormal results at EUS, elastography, ePFT and compliance of the main pancreatic duct. CONCLUSIONS: A multimodal EUS-based test for the morphological and functional evaluation of the pancreas is presented, which allows detecting mild pancreatic abnormalities in patients with suspected early chronic pancreatitis. The presence of abnormal morphological and functional evaluation of the pancreas could support the clinical suspicion of early chronic pancreatitis in the appropriate clinical setting.

Life with the pancreas: A personal experience.

This review article has primary objective to summarize pancreatic research which has been done in our laboratory since 1965, the first year of the author's registration in the Ph.D. program at the University of Sherbrooke (Canada). It covers the following major topics of pancreatic physiology: controls of pancreatic adaptation to diet, control of pancreatic enzyme secretion, control of pancreatic enzyme synthesis, control of pancreatic growth, intracellular events stimulated during pancreatic growth, pancreas regeneration after pancreatitis and pancreatectomy, the pancreatic cholecystokinin receptor types 1 and 2, growth control and cell signaling in pancreatic cancer cells and finally, cystic fibrosis.

Larimichthys crocea is a suitable bioindicator for monitoring short-term Cd discharge along the coast: An experimental study.

The present study evaluated the feasibility of using a marine cage fish Larimichthys crocea as a model for monitoring short-time Cd discharge near the sewage outlet. Fish were exposed to 0, 20, 100, 500 and 2500 µg/L for 6 h. Cd concentrations in gills, and left and right lobes of hepatopancreas were examined as well as activity levels of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathion-S-transferase (GST), glutathione reductase (GR), lipid peroxidation, glutathione (GSH) and mRNA levels of 19 genes encoding these enzymes. Cd concentrations increased at 100, 500 and 2500 µg/L Cd in gill and at 2500 µg/L Cd in hepatopancreas. Lipid peroxidation increased and GSH levels declined in gills at 2500 µg/L Cd. On the contrary, oxidative damage was not observed in hepatopancreas but GSH levels increased at all tested concentrations of Cd in the left lobe and at 20 µg/L Cd in the right lobe. The enhanced antioxidant response was confirmed in gills due to the increased activity levels of antioxidant enzymes and the up-regulated mRNA levels of most genes. However, disordered antioxidant response was observed in hepatopancreas, showing a dose- and lobe-dependent effect. RNA-seq and q-PCR analyses were performed to investigate differently expressed genes between both lobes under different concentrations of Cd. The most significantly enriched pathway term was pancreatic secretion, where the right lobe showed higher mRNA levels of 18 genes encoding pancreatic digestive enzymes than the left one under Cd stress. Interestingly, both lobes had the same mRNA levels of digestive enzyme genes and antioxidant genes in fish without Cd exposure. Overall, Larimichthys crocea is very sensitive to environmental exposure to cadmium. The present study for the first time investigates Cd-induced antioxidant response in Larimichthys crocea, also is the first to find lobe-dependent effects in fish.

Implication of neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function in diabetic gastroparesis.

Recently, diabetic gastroparesis (DGP) has received much attention as its prevalence is increasing in a dramatic fashion and management of patients with DGP represents a challenge in the clinical practice due to the limited therapeutic options. DGP highlights an interrelationship between the gastric emptying and pancreatic secretory function that regulate a wide range of digestive and metabolic functions, respectively. It well documented that both gastric emptying and pancreatic secretion are under delicate control by multiple neurohormonal mechanisms including extrinsic parasympathetic pathways and gastrointestinal (GI) hormones. Interestingly, the latter released in response to various determinants that related to the rate and quality of gastric emptying. Others and we have provided strong evidence that the central autonomic nuclei send a dual output (excitatory and inhibitory) to the stomach and the pancreas in response to a variety of hormonal signals from the abdominal viscera. Most of these hormones released upon gastric emptying to provide feedback, and control this process and simultaneously regulate pancreatic secretion and postprandial glycemia. These findings emphasize an important link between gastric emptying and pancreatic secretion and its role in maintaining homeostatic processes within the GI tract. The present review deals with the neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function that implicated in DGP and this provides new insights in our understanding of the pathophysiology of DGP. This also enhances the process of identifying potential therapeutic targets to treat DGP and limit the complications of current management practices.

[Effect of different nutritional support on pancreatic secretion in acute pancreatitis]. / Vliianie raznykh sposobov nutritivnoi podderzhki na sekretsiiu zhelezy pri ostrom pankreatite.

AIM: To develop and justify optimal nutritional support in early phase of acute pancreatitis (AP). MATERIAL AND METHODS: 140 AP patients were enrolled. They were divided into groups depending on nutritional support: group I (n=70) - early enteral tube feeding (ETF) with balanced mixtures, group II (n=30) - early ETF with oligopeptide mixture, group III (n=40) - total parenteral nutrition (TPN). The subgroups were also isolated depending on medication: A - Octreotide, B - Quamatel, C - Octreotide + Quamatel. Pancreatic secretion was evaluated by using of course of disease, instrumental methods, APUD-system hormone levels (secretin, cholecystokinin, somatostatin, vasointestinal peptide). RESULTS: ETF was followed by pancreas enlargement despite ongoing therapy, while TPN led to gradual reduction of pancreatic size up to normal values. α-amylase level progressively decreased in all groups, however in patients who underwent ETF (I and II) mean values of the enzyme were significantly higher compared with TPN (group III). Secretin, cholecystokinin and vasointestinal peptide were increasing in most cases, while the level of somatostatin was below normal in all groups. CONCLUSION: Enteral tube feeding (balanced and oligopeptide mixtures) contributes to pancreatic secretion compared with TPN, but this negative impact is eliminated by antisecretory therapy. Dual medication (Octreotide + Quamatel) is more preferable than monotherapy (Octreotide or Quamatel).

Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes.

Diabetes is a disease caused by a breakdown in the glucose metabolic process resulting in abnormal blood glucose fluctuations. Traditionally, control has involved external insulin injection in response to elevated blood glucose to substitute the role of the beta cells in the pancreas which would otherwise perform this function in a healthy individual. The central nervous system (CNS), however, also plays a vital role in glucose homoeostasis through the control of pancreatic secretion and insulin sensitivity which could potentially be used as a pathway for enhancing glucose control. In this review, we present an overview of the brain regions, peripheral nerves and molecular mechanisms by which the CNS regulates glucose metabolism and the potential benefits of modulating them for diabetes management. Development of technologies to interface to the nervous system will soon become a reality through bioelectronic medicine and we present the emerging opportunities for the treatment of type 1 and type 2 diabetes.

Correlation study between vitamin D level and glucose metabolism,lipid metabolism,insulin resistance,early ;secretory function of pancreatic islets in postmenopausal women with type 2 diabetes / 中国基层医药

Objective To investigate correlation between vitamin D and glucose metabolism,lipid metabolism, insulin resistance,early secretory function of pancreatic islets in postmenopausal women with type 2 diabetes. Methods 115 postmenopausal women with type 2 diabetes were selected as observation group.115 postmenopausal women without type 2 diabetes were selected in hospital at same period as control group.All patients received detection of vitamin D,glucose metabolism,lipid metabolism,insulin resistance,early secretory function of pancreatic islets. Correlation between vitamin D and glucose metabolism,lipid metabolism,insulin resistance,early secretory function of pancreatic islets were analyzed.Results Fasting blood glucose,postprandial 2h blood glucose,glycosylated hemoglobin, body mass index,total cholesterol,triglyceride,low density lipoprotein cholesterol,insulin resistance index in the observation group were higher than the control group [(8.5 ±1.2)mmol/L vs (5.1 ±0.6)mmol/L,(13.4 ± 1.5)mmol/L vs (7.8 ±0.7)mmol/L,(8.7 ±1.1)% vs (5.6 ±0.5)%,(25.7 ±1.0)kg/m2 vs (22.3 ±0.4)kg/m2 , (5.6 ±0.7)mmol/L vs (4.5 ±0.4)mmol/L,(2.3 ±0.5)mmol/L vs (1.7 ±0.3)mmol/L,(3.5 ±0.6)mmol/L vs (2.2 ±0.4)mmol/L,(3.6 ±0.5)vs (2.5 ±0.4),t =9.667,10.179,8.535,4.524,5.443,6.529,8.909,7.406, all P <0.05].High density lipoprotein cholesterol,insulin first secretion phase peak factor,pancreatic islet βcell function index,fasting insulin,vitamin D in the observation group were lower than the control group [(1.0 ± 0.2)mmol/L vs (1.2 ±0.3)mmol/L,(5.2 ±1.3)vs (8.4 ±1.6),(135.8 ±11.7)vs (194.3 ±19.2),(4.1 ± 0.9)IU /mL vs (10.8 ±0.6)IU /mL,(10.8 ±2.1)ng/L vs (27.4 ±3.8)ng/L,t =5.087,9.153,7.370,10.414, 18.371,all P <0.05].Vitamin D was significantly negatively correlated with fasting blood glucose,postprandial 2h blood glucose,glycosylated hemoglobin,body mass index,total cholesterol,triglyceride,low density lipoprotein choles-terol,insulin resistance index(r =-0.537,-0.512,-0.469,-0.387,-0.325,-0.316,-0.372,-0.457,all P <0.05).Vitamin D were significantly positively correlated with high density lipoprotein cholesterol,insulin first secretion phase peak factor,pancreatic islet βcell function index,fasting insulin(r =0.351,0.418,0.674,0.316,all P <0.05).Conclusion Vitamin D deficiency in postmenopausal women with type 2 diabetes may be involved in glucose -lipid metabolism and insulin resistance,but also may be one of the reasons leading to decreasing of early secretory function of pancreatic βcells.

Clinical management of post-pyloric enteral feeding in children.

Post-pyloric feeding (PF) allows the administration of enteral nutrition beyond the pylorus, either into the duodenum or, ideally, into the jejunum. The main indications of PF are: upper gastrointestinal tract obstructions, pancreatic rest (e.g., acute pancreatitis), gastric dysmotility (e.g., critically ill patients and chronic intestinal pseudo-obstruction) or severe gastroesophageal reflux with risk of aspiration (e.g., neurological disability). Physiological and clinical evidence derives from adults, but can also be pertinent to children. This review will discuss the practical management and potential clinical applications of PF in pediatric patients. Some key studies pertaining to the physiological changes during PF will also be considered because they support the strategy of PF management.

Mnk1 is a novel acinar cell-specific kinase required for exocrine pancreatic secretion and response to pancreatitis in mice.

OBJECTIVE: Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription factor 1 (PTF1) complex. Induction of pancreatitis leads to MAP kinase activation and transient suppression of the acinar differentiation programme. We investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. DESIGN: Mnk1 expression was analysed using immunohistochemistry, RT-qPCR and western blotting. Ptf1a binding to Mnk1 was assessed by chromatin immunoprecipitation and qPCR. Acute pancreatitis was induced in wild type and Mnk1(-/-) mice by 7 h intraperitoneal injections of caerulein. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. In vivo secretion was quantified by secretin-stimulated MRI. RESULTS: Mnk1 is expressed at the highest levels in pancreatic acinar cells and is a direct PTF1 target. Mnk1 is activated upon induction of pancreatitis and is indispensable for eIF4E phosphorylation. The pancreas of Mnk1(-/-) mice is histologically normal. Digestive enzyme content is significantly increased and c-Myc and Ccnd1 levels are reduced in Mnk1(-/-) mice. Upon induction of acute pancreatitis, Mnk1(-/-) mice show impaired eIF4E phosphorylation, activation of c-Myc and downregulation of zymogen content. Acinar cells show defective relocalisation of digestive enzymes, polarity defects and impaired secretory response in vitro and in vivo. CONCLUSIONS: Mnk1 is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and eIF4E phosphorylation. It is required for the physiological secretory response of acinar cells and for the homeostatic response to caerulein administration during acute pancreatitis.

EFFECT OF ENDURANCE TRAINING ON PANCREATIC EXOCRINE RESPONSE TO CHOLECYSTOKININ (CCK) IN RATS / 体力科学

In the previous studies, we found that endurance training increased pancreatic weight, protein content, and enzyme activity with hypertrophied acinar cells in rats. The purpose of the present study was to investigate the effect of endurance training on pancreatic exocrine response to CCK in rats. Female F344 rats were divided into control (C, n=6) and endurance training (T, n=6) groups. The trained rats were exercised for 60 min on a treadmill (final speed, 35 m/min), 5 days a week, for 8 weeks. Food intake in both groups was matched. On the final day of the experiment, the rats were anesthetized after an overnight fast and prepared with cannulae into the pancreatic duct. After 1-h basal collection with 0.9% NaCl (7.5 ml/kg body weight/h) injected intravenously, CCK-8 (0.06μg/kg body weight/h) was injected intravenously and pancreatic secretions were collected for the additional three 1-h periods. Final body weight in the T group was slightly, but not significantly, lower than in the C group (C : 145±6, T : 137±8 g). Pancreatic wet weight in the T group was significantly higher than in the C group (C : 4.14±0.16, T : 4.71±0.18 mg/g BW). CCK-stimulated pancreatic juice secretion was not significantly changed. There were significant increases in pancreatic protein and amylase secretions with CCK administration. CCK-stimulated pancreatic protein and amylase secretions were significant higher in the T group than in the C group. Total pancreatic protein secretion with CCK administration during 3 hours were significant higher in the T group than in the C group (C : 2.52±1.92, T : 5.11±1.50 mg/3 h). Total amylase secretion with CCK administration during 3 hours were also significant higher in the T group than in the C group (C : 0.69±0.43, T : 1.12±0.37 U/3 h). These results suggest that the endurance training increased pancreatic exocrine secretion response to CCK. CCK may play an important role in exercise-induced enhancement of the exocrine pancreas.

Roles of Gonadal Steroids on Exocrine Secretion of Isolated Perfused Rat Pancreas

To clarify the roles of gonadal steroids on pancreatic exocrine secretion, effects of progesterone and estradiol-17beta on spontaneous and secretagogue-induced exocrine response of isolated perfused rat pancreas were investigated. Intra-arterial infusion of progesterone resulted in significant increase of the spontaneous pancreatic fluid and amylase secretion dose-dependently. However, estradiol-17beta did not exert any influence on spontaneous pancreatic exocrine secretion. Exogenous secretin, cholecystokinin (CCK), and acetylcholine markedly stimulated pancreatic fluid and amylase secretion. Progesterone initially enhanced secretin-induced amylase secretion, but this stimulatory response declined thereafter to basal value. Moreover, secretin-induced fluid secretion was not affected by infusion of progesterone. Therefore, initial increase of secretion-induced amylase secretion by progesterone seems to be a non-specific action by washout effect of secretin. Estradiol-17beta failed to change the secretin-induced fluid and amylase secretion. Both progesterone and estradiol-17beta did not exert any influence on CCK-induced fluid and amylase secretion. Acetylcholine-induced exocrine secretion of isolated perfused pancreas also was not affected by intra-arterial infusion of progesterone or estradiol-17beta. It is concluded from the above results that progesterone could enhance the spontaneous pancreatic fluid and amylase secretion of isolated perfused rat pancreas through non-genomic short- term action, and that these effects could be masked by more potent stimulants such as secretin, CCK, and acetylcholine.

A role of endogenous somatostatin in exocrine secretion induced by intrapancreatic cholinergic activation

A role of endogenous somatostatin in pancreatic exocrine secretion induced by intrapancreatic cholinergic activation was studied in the isolated rat pancreas perfused with modified Krebs-Henseleit solution. Intrapancreatic neurons were activated by electrical field stimulation (EFS: 15 V, 2 msec and 8 Hz). Pancreatic exocrine secretion, including volume flow and amylase output, and release of somatostatin from the pancreas were respectively determined. Somatostatin cells in the islet were stained with an immunoperoxidase method. EFS significantly increased pancreatic volume flow and amylase output, which were reduced by atropine by 59% and 78%, respectively. Intraarterial infusion of either pertussis toxin or a somatostatin antagonist resulted in a further increase in the EFS-evoked pancreatic secretion. EFS also further elevated exocrine secretion in the pancreas treated with cysteamine, which was completely restored by intraarterial infusion of somatostatin. EFS significantly increased not only the number of immunoreactive somatostatin cells in the islet but also the concentration of immunoreactive somatostatin in portal effluent. It is concluded from the above results that intrapancreatic cholinergic activation elevates pancreatic exocrine secretion as well as release of endogenous somatostatin. Endogenous somatostatin exerts an inhibitory influence on exocrine secretion induced by intrapancreatic cholinergic activation via the islet-acinar portal system in the isolated pancreas of the rat.