Pancreatic secretory response to feeding in the calf: CCK-A receptors, but not CCK-B/gastrin receptors are involved

In bovine species, as in human, the pancreas predominantly expresses cholecystokinin-B (CCK-B)/gastrin receptors. However, the role of this receptor in the regulation of meal-stimulated pancreatic enzyme release has not been determined. In milk-fed calves, we previously described prandial patterns of exocrine pancreatic secretion and a long prefeeding phase was observed. The present study was aimed at determining both the role of external stimuli in the outset of the prefeeding phase and the implication of pancreatic CCK-A and CCK-B/gastrin receptors in the mediation of pancreatic response to feeding. The first objective was studied by suppressing external stimuli associated with food intake (unexpected meal) and the second by infusing highly specific and potent antagonists of CCK-A (SR 27897) and CCK-B/gastrin (PD 135158) receptors during the prandial period. When calves were given an unexpected meal, the long prefeeding increase in pancreatic secretion was absent. SR 27897 (but not PD 135158) inhibited the preprandial phase and greatly reduced postprandial pancreatic juice and enzyme outflows. The expectancy of a meal seemed to elicit an increased pancreatic response right before a meal and CCK-A receptors may mediate this information via neural pathways. The implication of CCK and CCK-A receptors in mediating the postfeeding pancreatic response was also demonstrated. The participation of CCK-B/gastrin receptors in this regulation was not demonstrated.     

The effect of oleate on pancreatic and bile secretion in the conscious rat

The effects of sodium oleate infused into either the duodenum or the terminal ileum on bile and pancreatic secretion were examined in the conscious rat. Rats were prepared with cannulae draining pure bile and pancreatic juice separately, and with an ileal and two duodenal cannulae. A 40 mM taurocholate solution containing 7 mg/ml bovine trypsin was infused into the duodenum throughout the experiment to replace diverted bile-pancreatic juice to maintain the normal regulation of pancreatic secretion. The intraduodenal infusion of sodium oleate significantly increased pancreatic juice flow, protein, and bicarbonate outputs, whereas it did not affect bile secretion. Intravenous infusion of proglumide (300 mg/kg/hr) did not inhibit pancreatic secretion stimulated by intraduodenal infusion of sodium oleate. An intravenous infusion of atropine (100 micrograms/kg/hr) attenuated protein and fluid secretions but not that of bicarbonate in response to intraduodenal oleate. In contrast, the intraileal infusion of oleate had no effect on pancreatic secretion, whereas it decreased bile flow, bicarbonate, and bile salt outputs. In conclusion, sodium oleate introduced in the duodenum stimulates pancreatic secretion but oleate in the terminal ileum inhibits bile secretion.     

吗啡和纳洛酮对酸化十二指肠引起狗胰液分泌的影响

本工作用制备 Thomas 胰瘘和胃痿的5条狗进行慢性实验。实验时用0.1N 盐酸灌入十二指肠以刺激胰液分泌,并分別注射吗啡或/和纳洛酮,观察它们对胰液分泌和对胰液中碳酸氢盐和蛋白质浓度的影响。另外我们还观察了吗啡和纳洛酮对6条狗离体胰主导管紧张性的影响。结果表明:(1)吗啡抑制了胰液分泌量,对胰液中碳酸氢盐和蛋白质浓度无影响,由于分泌量减少故两者的排出量显著减少(P<0.05),(2)纳洛酮本身对胰液分泌量和碳酸氢盐及蛋白质浓度均无影响;(3)纳洛酮可以加强吗啡抑制胰液分泌的作用(P<0.01);(4)吗啡能增加狗的离体胰主导管肌条的紧张性,纳洛酮不能阻断或翻转吗啡的这一效应,相反能加强其效应。本工作表明,吗啡抑制酸化十二指肠所引起的胰碳酸氢盐和蛋白质排出量,其机制可能是吗啡刺激胰导管收缩,而纳洛酮则加强吗啡的这种抑制效应。     

Caerulein and secretin induced pancreatic growth: a possible control by endogenous pancreatic somatostatin

Pancreatic hypertrophy and hyperplasia following chronic joint (CA + SE), or separate, caerulein (CA: 1 microgram . kg-1) and secretin (SE: 75 micrograms . kg-1) administration were studied in parallel with pancreatic somatostatin (SRIF) contents following 2, 4, 7 and 10 days of treatment. Parameters indicative of pancreatic growth (tissue weight, DNA and protein contents, cellular protein concentrations) increased significantly after 2 days of CA or CA + SE and reached a plateau between days 4 and 10. SE merely induced a mild hypertrophy after 4 days. Endogenous pancreatic SRIF contents varied upon treatment, differently so with each peptide regimen. Indeed, CA and CA + SE treatments decreased total SRIF contents after 2 days with no effect thereafter. SE also decreased the latter after 2 days while significant increases were observed after 7 and 10 days. The inverse relationship seemingly existing between SRIF contents and the amplitude of hormonally-induced pancreatic growth supports the hypothesis that endogenous pancreatic SRIF, operating as an 'antigrowth' factor, may participate in the exogenous CA, SE and CA + SE stimulated pancreatic growth phenomena.     

Two hypotheses on the feedback regulation of pancreatic enzyme secretion

We review the mechanisms underlying the feedback regulation of pancreatic enzyme secretion in response to a meal. Pancreatic enzyme secretion in the rat and pig is known to be regulated by a negative feedback mechanism mediated by intestinal trypsin and chymotrypsin. Such a mechanism has recently been noted in humans. The presence of these enzymes in the small intestine suppresses pancreatic enzyme secretion, whereas their removal increases it. Two novel peptides have been proposed to account for the stimulation of pancreatic enzyme secretion in response to feeding trypsin inhibitor. One was assumed to be present in rat pancreatic juice and the other to be spontaneously secreted from the rat small intestine. In either case, trypsin and trypsin inhibitors do not directly interact with the luminal surface of the small intestine, but their actions are mediated by a trypsin-sensitive, cholecystokinin-releasing peptide. This is a novel explanation of the well-recognized stimulation of pancreatic enzyme secretion in response to dietary protein intake.     

Effect of glucagon on canine exocrine pancreatic secretion stimulated by a test meal

The effect of glucagon on exocrine pancreatic secretion stimulated by a test meal was studied in three dogs with a chronic gastric fistula and a modified Thomas duodenal fistula which allows easier collection of pure pancreatic juice after a meal. Glucagon was given by continuous intravenous infusion in doses of 5, 10, 15, or 30 microgram/kg per hour, before and during a test meal. At each dose level glucagon significantly reduced the water and electrolyte secretion of the pancreas. At 15 and 30 microgram/kg per hour glucagon inhibited protein output; this effect was absent at lower doses. These findings demonstrate a dose-dependent inhibition by glucagon of the pancreatic bicarbonate and protein response to a meal. Inhibition of bicarbonate output was more sensitive to glucagon than that of protein output.     

The importance of gastric secretion in the feedback control of interdigestive and postprandial pancreatic secretion in rats.

Previous studies demonstrated that pancreatic enzyme secretion in rats is stimulated by the diversion of pancreatic juice from the duodenum or by the inhibition of pancreatic proteinases in the intestinal lumen but little attention has been paid to the role of gastric secretion in this stimulation. This study, carried out on conscious rats with large gastric (GF) and pancreatic fistulas, confirms that diversion of pancreatic juice in rats with the GF closed results in the progressive stimulation of pancreatic secretion reaching the maximum similar to that induced by exogenous CCK. When the GF was kept open, the diversion resulted in only small increment in pancreatic secretion and this was accompanied by progressive increase in gastric acid outputs. Similar amounts of HCl (25-400 mumol/h) instilled intraduodenally (i.d.) in rats with the GF open fully reproduced the increase in pancreatic secretion observed after the diversion of pancreatic juice and this effect was completely abolished by the pretreatment with L-364,718, a specific CCK receptor antagonist. Pretreatment with omeprazole to suppress completely gastric acid secretion in the diverted state resulted in a decline in pancreatic secretion similar to that observed after opening the GF. Camostate given in graded doses (6-200 mg/kg) either i.d. or s.c. in rats with pancreatic juice returned to the duodenum caused a dose-dependent increase in pancreatic secretion, but after opening the GF or after omeprazole this increase was reduced by about 50% while after L-364,718 it was abolished. This study provides evidence that gastric secretion plays an important role in the pancreatic response to diversion of pancreatic juice or inhibition of luminal proteinases (but not to feeding) and the elimination of gastric acid reduces this response.     

Meal-stimulated exocrine pancreatic secretion and release of GI peptides in normal and nicotine-treated rats

In rats, treated chronically with saline and nicotine, we studied the postprandial release of gastrin and cholecystokinin by specific radioimmunoassays and simultaneously measured secretory outputs of the exocrine pancreas. Rats were prepared surgically with gastric and pancreatic fistulas. Meal-stimulated release of peptides and exocrine secretory outputs were measured 24 h postoperatively in conscious rats. Infusion of food via intragastric cannula significantly stimulated plasma gastrin levels in both control and nicotine treated rats. Postprandial gastrin levels in nicotine treated rats were significantly higher compared to gastrin levels obtained after food in untreated control rats. Plasma CCK levels were increased in both groups after food. These levels remained significantly elevated from the basal values only for a transient period following infusion of the liquid meal. There were no differences in postprandial plasma CCK levels between the two groups. Outputs of exocrine pancreatic volume, protein and trypsin increased significantly after food in both control and nicotine treated groups of rats. The differences in outputs of volume and protein between the two groups of rats were not significant; however, the trypsin outputs in the nicotine rats were decreased significantly when compared to control rats. The data indicate that in rats, administration of food stimulated the release of immunoreactive gastrin and CCK with concomitant increase in exocrine pancreatic secretions of volume, protein and trypsin. Chronic nicotine treatment and its effect on food, however, appeared to have induced hyperfunction of G-cells that resulted in increased gastrin secretion and a decrease in trypsin secretion by exocrine pancreas. These data may have important implications in the etiology of the development of exocrine pancreatic dysfunction in chronic smokers.     

Role of histamine H2-receptors in gastric and pancreatic release of somatostatin-like immunoreactivity during the gastric phase of a meal

The present study was designed to determine the role of H₂-receptors in the postprandial release of somatostatin-like immunoreactivity (SLI) from the gastric fundus and antrum and from the pancreas. In dogs subjected to laparotomy, the pylorus was bisected and a gastric fistula was created, following which 250 ml 20% liver extract (LE) at pH 7 or 2 were instilled intragastrically. In the fundic vein the incremental SLI rise in response to LE at pH 7 was 2423 ± 540 pg/ml during a control infusion of saline and 4780 ± 863 pg/ml during the infusion of cimetidine (1 mg/kg per h) (P < 0.05). In the antral vein the incremental SLI in response to LE at pH 7 was 2182 ± 530 pg/ml during the saline control but did not rise significantly during cimetidine infusion. In the pancreatic vein the incremental SLI level after LE at pH 7 was 1953 ± 358 pg/ml in the control experiments and 4430 ± 1024 pg/ml during cimetidine infusion (P < 0.025). The incremental inferior vena cava SLI level was approximately 925 pg/ml in both groups (not significant).The instillation of LE at pH 2 during the saline control lowered fundic vein SLI by 500 pg/ml; this decline was abolished during cimetidine infusion. In the antral vein the incremental SLI level of 15 750 ± 2514 pg/ml during saline was lowered to only 6728 ± 2257 pg/ml during cimetidine (ifP < 0.025). After LE at pH 2 the incremental pancreatic vein SLI level of if5641 ± to be one regulatory component in the modulation of gastric acid secretion and gastrin release [21,26] during the gastric phase of a meal. The possible involvement of H₂-receptors in this regulatory system is schematized in Fig. 7.Pancreatic SLI release is also influenced by H₂-receptors but this appears to depend on the intragastric pH; stimulation of the receptors appears to lower the pancreatic SLI response to neutral protein and raise the response to acidified protein. If these effects are due to stimulation of gastric and/or pancreatic H₂-receptors can not be determined from the present data.These findings, in conjunction with previous studies [21–25], reveal a highly complex regulatory system for somatostin release during the gastric phase of meal, and indicate that, in addition to the influence of muscarinic-cholinergic [23], adrenergic mechanisms [24] and prostaglandins [25], reveal a histaminergic influence must now be recognized.     

Responses of the exocrine pancreatic secretion to spontaneous feeding in rats with bile-pancreatic juice diversion

The regulatory response of the exocrine pancreas was examined in rats under unanesthetized and unrestrained conditions. The previous study demonstrated that the pancreatic protease secretion increased 2-fold after spontaneous feeding of a low protein diet in chronically bile-pancreatic cannulated rats (normal rats) whose bile-pancreatic juice (BPJ) was returned to the duodenum. In the present study, we observed the response of the exocrine pancreatic secretion to spontaneous feeding of a low protein diet in rats with chronic diversion of BPJ from the proximal small intestine for 6 days (bypass rat) whose diverted BPJ was returned to the upper ileum. During BPJ diversion, the dry weight and the protein content of the pancreas were increased 2-fold, compared with normal rats. Also, the levels of trypsinogen and chymotrypsinogen in the pancreas were increased several times, but amylase was decreased. The basal secretion of enzymes after a 24-hr fast was enhanced in bypass rats in proportion to the pancreatic enzyme contents. After spontaneous feeding of 8% casein fat-free diet, the increases in the pancreatic secretion of bypass rats were much smaller than those of normal rats. In contrast, the increase of BPJ flow of bypass rats after feeding was greater than that of normal rats. These findings represent that the chronic diversion of BPJ exerts hypergrowth of pancreas and hypersecretion of proteases in the fasting state, and less sensitivity of pancreatic enzyme secretion to dietary feeding.     

Influence of vagotomy on glucose tolerance and on the responses of plasma insulin and exocrine pancreatic function followed glucose load or food ingestion in dogs]

A part of the intrapancreatic nerve fibres of dogs show 1-2 months after bilateral truncal vagotomy a decay of the medullary sheath; in addition, the histochemically demonstrable insulin content of the B-cells is reduced. These animals do no longer react to oral glucose administration or feeding a meat meal with a reflectoric early rise of plasma insulin concentration and of exocrine functional parameters (all the animals were bearing exocrine pancreas fistulas). The glucose tolerance and and the decrease of free fatty acids in serum were restricted. Also, the content of bicarbonate and protein in the pancreatic juice and the insulin secretion of vagotomized animals are strongly reduced in the subsequent test phase (up to 120 min) following oral or i.v. glucose administration and after feeding meat. The inhibition of exocrine volume secretion following i.v. glucose administration was enhanced by the intervention. The findings confirm the involvement of the N. vagus in the mechanisms of the enteroinsular axis that becomes active together with exocrine gastro- and duodenopancreatic reflexes to any kind of physiological enteral stimulation.     

Exogenous leptin inhibits the secretion of pancreatic juice via a duodenal CCK1-vagal-dependent mechanism in anaesthetized rats

Leptin originally described as product of the ob gene has been shown to be expressed in various tissues including the gastrointestinal tract. In this study, we investigated the influence of leptin on the secretion of pancreatic juice in biliary-pancreatic duct cannulated anaesthetised rats and in dispersed rat pancreatic acini in vitro. Exogenous leptin was given in boluses intravenously with or without CCK-8 (12 pmol kg(-1) body weight) in the presence or absence pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. Administration of leptin (0.1, 1 and 10 microg kg(-1) body weight) did not affect the volume of bile and pancreatic juice while the protein and trypsin outputs were reduced in a dose-dependent manner. In the rats, leptin inhibited CCK-8 stimulated protein and trypsin outputs stronger than the basal pancreatic secretion. The inhibition by leptin was abolished by the pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. In contrast, leptin did not affect basal and CCK-8-stimulated amylase release from the dispersed rat pancreatic acini in vitro. In conclusion, the results of the present study suggest that leptin does not act directly on the rat pancreatic acinar cells but inhibits the secretion of pancreatic enzymes acting indirectly via a neurohormonal CCK-vagal-dependent mechanism.     

Plasma Somatostatin-like immunoreactivity in chemically sympathectomized dogs

The present study was designed to determine the role of the adrenergic nerves upon basal and postprandial gastric and pancreatic SLI release. In 19 chemically sympathectomized dogs peripheral venous plasma SLI levels in the basal and postprandial state were significantly below those of 30 controls for the first 135 min after the ingestion of a fat-protein meal. To determine the origin of this reduction, the SLI release from fundus, antrum and pancreas was studied in anesthetized dogs during the gastric phase of a meal at either pH 7 or pH 2. In response to a liver meal at pH 7 fundic, antral and pancreatic vein SLI levels were below the control and the rise in inferior vena cava SLI was abolished. In response to a liver meat at pH 2, the rise in antral and pancreatic vein SLI as clearly reduced in the sympathectomized dogs, while the decrease in fundic SLI was not influenced. The data demonstrate that adrenergic innervation plays a role in basal and postprandial SLI release from the stomach and pancreas.     

Role of cholecystokinin in the intestinal fat- and acid-induced inhibition of gastric secretion.

This study was designed to determine the role of cholecystokinin (CCK) in the inhibition of gastric HCl secretion by duodenal peptone, fat and acid in dogs with chronic gastric and pancreatic fistulas. Intraduodenal instillation of 5% peptone stimulated both gastric HCl secretion and pancreatic protein secretion and caused significant increments in plasma gastrin and CCK levels. L-364,718, a selective antagonist of CCK-A receptors, caused further increase in gastric HCl and plasma gastrin responses to duodenal peptone but reduced the pancreatic protein outputs in these tests by about 75%. L-365,260, an antagonist of type B receptors, reduced gastric acid by about 25% but failed to influence pancreatic response to duodenal peptone. Addition of 10% oleate or acidification of peptone to pH 3.0 profoundly inhibited acid secretion while significantly increasing the pancreatic protein secretion and plasma CCK levels. Administration of L-364,718 reversed the fall in gastric HCl secretion and significantly attenuated pancreatic protein secretion in tests with both peptone plus oleate and peptone plus acid. Exogenous CCK infused i.v. in a dose (25 pmol/kg per h) that raised plasma CCK to the level similar to that achieved by peptone meal plus fat resulted in similar inhibition of gastric acid response to that attained with fat and this effect was completely abolished by the pretreatment with L-364,718. We conclude that CCK released by intestinal peptone meal, containing fat or acid, exerts a tonic inhibitory influence on gastric acid secretion and gastrin release through the CCK-A receptors.     

Feedback control of pancreatic secretion in rats. Role of gastric acid secretion.

Pancreatic secretion in rats is regulated by feedback inhibition of cholecystokinin (CCK) release by proteases in the gut lumen, but little is known about the role of gastric acid in this regulation. This study, carried out on conscious rats with large gastric fistulas (GF) and pancreatic fistulas, shows that diversion of pancreatic juice results in the progressive stimulation of pancreatic secretion only in rats with the GF closed. When the GF was kept open, the diversion resulted in only small increment in pancreatic secretion and this was accompanied by progressive increase in gastric acid outputs. Similar amounts of HCl instilled into the duodenum in rats with the GF open fully reproduced the increase in pancreatic secretion observed after the diversion of pancreatic juice. Pretreatment with omeprazole (15 mumol/kg) to suppress gastric acid secretion or with L-364,718 (5 mumol/kg) to antagonize CCK receptors in the diverted state, resulted in the decline in pancreatic secretion similar to that observed after opening the GF. CCK given s.c. (20-320 pmol/kg) failed to cause any significant rise in the post-diversion pancreatic secretion in rats with the GF closed, but stimulated this secretion dose-dependently when the GF was open. Camostate (6-200 mg/kg) in rats with pancreatic juice returned to the duodenum caused dose-dependent increase in pancreatic secretion, but after opening the GF or after omeprazole this increase was reduced by about 75%. This study provides evidence that gastric acid plays a crucial role in the pancreatic response to diversion of pancreatic juice or inhibition of luminal proteases, and that factors that eliminate gastric acid secretion reduce this response.     

Neurotensin modulates the composition of pancreatic exocrine secretions in chickens

The effects of neurotensin on pancreatic exocrine secretion were examined in fasted, conscious White Leghorn hens. A cannula was surgically implanted in the central duct serving the ventral lobe of the pancreas in order to collect pure pancreatic juice. Following recovery, neurotensin was infused intravenously at 3.6 or 10.8 pmol/kg*min. The volume and pH of the pancreatic secretions were recorded and total pancreatic protein concentration, amylase, lipase, trypsin, and chymotrypsin activity were measured every 30 min for 2 hr and compared to secretions following the infusion of 0.9% saline. Our results demonstrated that neurotensin did not affect the pH nor the pancreatic juice protein concentration, but did increase secretion rate following neurotensin infusion at 3.6 pmol/kg*min. Amylase activity was significantly depressed during neurotensin infusions, while lipase (both pancreatic and carboxylester lipase) activity was significantly elevated. The ratio of amylase to lipase activity was especially depressed by neurotensin infusion at 10.8 pmol/kg*min. Insufficient secretory activity prevented a balanced statistical analysis of chymotrypsin activity, but from a pooled analysis, neurotensin had no effect on protease activity in the pancreatic juice. These results support our current research indicating that neurotensin may be a hormonal regulator of postprandial lipid digestion in chickens.     

Carbohydrates modulate opiate receptor mediated mechanisms during postprandial endocrine function

The present study was designed to determine the role of carbohydrates during naloxone-induced opiate receptor blockade upon the postprandial rise of plasma somatostatin (SLI), insulin and pancreatic polypeptide (PP) levels in response to protein and fat test meals in conscious dogs. Test meals consisting of 50 g liver extract + 50 g sucrose or 50 g corn oil + 50 g sucrose dissolved in 300 ml water were instilled intragastrically, respectively. Additionally, liver extract and fat meals were given with a concomitant intravenous infusion of glucose. To all test meals either naloxone (4 mg) or saline was added. The addition of sucrose to liver extract or the infusion of i.v. glucose during the liver meal abolished the inhibitory effect of naloxone on the rise of postprandial somatostatin levels which has been described recently. The addition of carbohydrate either orally or intravenously to the fat meal resulted in an even stimulatory effect of naloxone upon the rise of postprandial somatostatin levels. Insulin levels were not changed during liver extract + sucrose or i.v. glucose, respectively. When sucrose or i.v. glucose was administered together with the fat meal the addition of naloxone augmented postprandial insulin secretion. Pancreatic polypeptide (PP) release was augmented during the combination of sucrose or i.v. glucose with the fat and liver meal when naloxone was present in the meals. The present data demonstrate that the addition of carbohydrates either orally or intravenously to fat and protein meals modulates the effect of endogenous opiates in the regulation of postprandial somatostatin, insulin and pancreatic polypeptide release in dogs in a way that carbohydrates induce inhibitory mechanisms that are mediated via endogenous opiate receptors.     

Intestinal fat suppresses protein-induced exocrine pancreatic secretion in chronically bile-pancreatic juice-diverted rats

Previously, we showed that the increase in pancreatic enzyme secretion was lower after feeding a casein diet containing fat than that after feeding a fat-free casein diet in chronically bile-pancreatic juice (BPJ)-diverted rats. In the present study, we determined whether the suppressive effects of fats on flow volume of BPJ and pancreatic enzyme secretion depend on delaying gastric emptying and examined the characteristics of the suppression with intraduodenal instillation of soybean oil or lecithin in BPJ-diverted rats. The study was conducted as three separate experiments using conscious rats with chronic BPJ diversion by means of a common bile-pancreatic duct catheter. The flow volume of BPJ and the secretion of pancreatic amylase and trypsin were determined after intraduodenal instillation of the test solution. Exocrine pancreatic secretion was strongly stimulated by administration of guanidinated casein hydrolysate (HGC, 150 mg/ml) in chronic BPJ-diverted rats. However, pancreatic secretion after administration of an emulsion containing HGC with either soybean oil (100 mg/ml) or mixed fat (50 mg/ml soybean oil + 50 mg/ml lecithin) was much lower than that after administration of HGC alone. In contrast, administration of the soybean oil emulsion without HGC resulted in a small, but significant increase in the volume of BPJ. The suppressive effects of soybean oil (100 mg/ml) on the increases in the BPJ flow and enzyme secretion were similar to those of sodium taurocholate (10 mg/ml), and there was no additive effect of soybean oil on taurocholate suppression. In conclusion, duodenally instilled soybean oil suppressed increases in flow volume of BPJ and pancreatic enzyme secretion induced by HGC in chronic BPJ-diverted rats, showing that the suppressive effect of the fat does not depend on delaying gastric emptying.     

Neurotensin stimulates pancreatic exocrine secretion in rats

Neurotensin (NT) stimulates pancreatic exocrine secretion in dogs and humans. The purpose of this study was to examine the effect of exogenous neurotensin on pancreatic exocrine secretion in rats. Five Sprague-Dawley male rats were prepared with pancreatic, gastric and duodenal fistulas. Bile was shunted into the duodenum in order to collect pure pancreatic juice. 24 h later, neurotensin (0.05, 0.1, 0.2, 0.3, 1.0 nmol/kg) was infused intravenously in a random fashion. Pancreatic juice was collected every 10 min, and the volume was recorded and protein and bicarbonate were measured. Neurotensin stimulated, in a dose-related manner, the pancreatic secretion of water, protein and bicarbonate. Neurotensin may be involved in the physiologic control of pancreatic secretion in rats.     

Role of leptin in the control of postprandial pancreatic enzyme secretion.

Leptin released by adipocytes has been implicated in the control of food intake but recent detection of specific leptin receptors in the pancreas suggests that this peptide may also play some role in the modulation of pancreatic function. This study was undertaken to examine the effect of exogenous leptin on pancreatic enzyme secretion in vitro using isolated pancreatic acini, or in vivo in conscious rats with chronic pancreatic fistulae. Leptin plasma level was measured by radioimmunoassay following leptin administration to the animals. Intraperitoneal (i.p.) administration of leptin (0.1, 1, 5, 10, 20 or 50 microg/kg), failed to affect significantly basal secretion of pancreatic protein, but markedly reduced that stimulated by feeding. The strongest inhibition has been observed at dose of 10 microg/kg of leptin. Under basal conditions plasma leptin level averaged about 0.15 +/- 0.04 ng/ml and was increased by feeding up to 1.8 +/- 0.4 ng/ml. Administration of leptin dose-dependently augmented this plasma leptin level, reaching about 0.65 +/- 0.04 ng/ml at dose of 10 microg/kg of leptin. This dose of leptin completely abolished increase of pancreatic protein output produced by ordinary feeding, sham feeding or by diversion of pancreatic juice to the exterior. Leptin (10(-10)-10(-7) M) also dose-dependently attenuated caerulein-induced amylase release from isolated pancreatic acini, whereas basal enzyme secretion was unaffected. We conclude that leptin could take a part in the inhibition of postprandial pancreatic secretion and this effect could be related, at least in part, to the direct action of this peptide on pancreatic acini.