Stimulatory effect of xenin-8 on insulin and glucagon secretion in the perfused rat pancreas

Xenin is a 25-amino acid peptide of the neurotensin/xenopsin family identified in gastric mucosa as well as in a number of tissues, including the pancreas of various mammals. In healthy subjects, plasma xenin immunoreactivity increases after meals. Infusion of the synthetic peptide in dogs evokes a rise in plasma insulin and glucagon levels and stimulates exocrine pancreatic secretion. The latter effect has also been demonstrated for xenin-8, the C-terminal octapeptide of xenin. We have investigated the effect of xenin-8 on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Xenin-8 stimulated basal insulin secretion and potentiated the insulin response to glucose in a dose-dependent manner (EC(50)=0.16 nM; R(2)=0.9955). Arginine-induced insulin release was also augmented by xenin-8 (by 40%; p<0.05). Xenin-8 potentiated the glucagon responses to both arginine (by 60%; p<0.05) and carbachol (by 50%; p<0.05) and counteracted the inhibition of glucagon release induced by increasing the glucose concentration. No effect of xenin-8 on somatostatin output was observed. Our observations indicate that the reported increases in plasma insulin and glucagon levels induced by xenin represent a direct influence of this peptide on the pancreatic B and A cells.     

Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion.

One of the peptides previously discovered in amphibians is the octapeptide xenopsin. As immunohistochemistry has also indicated the presence of xenopsin immunoreactivity in man, we extracted in the present investigation xenopsin-immunoreactive material from human gastric mucosa and purified it to homogeneity with several high performance liquid chromatography (HPLC) reverse phase and ion exchange chromatographic steps. The eluates were monitored with a radioimmunoassay for amphibian xenopsin. Determination of the amino acid sequence revealed a 25-amino acid peptide having 6 C-terminal amino acids in common with amphibian xenopsin. The sequence of this peptide, termed xenin 25, is M-L-T-K-F-E-T-K-S-A-R-V-K-G-L-S-F-H-P-K-R-P-W-I-L. The peptide was custom-synthesized. Mass spectrometry of the synthetic and the extracted peptide revealed identical molecular mass. Purification of 250 ml of human postprandial plasma with Sep-Pak C18 cartridges, reverse phase HPLC, and ion exchange chromatography demonstrated circulating xenin immunoreactivity at a retention time identical to xenin 25. The amount of xenin immunoreactivity at the position of xenin 25 on C18-HPLC increased significantly after a meal. A radioimmunoassay utilizing antibodies to xenin 25 and a 125I-labeled analogue of xenin 25 was used to measure immunoreactive xenin in the plasma of 10 volunteers. There was a significant rise of xenin immunoreactivity in the plasma after a meal. Intravenous infusion of the synthetic peptide in dogs stimulated exocrine pancreatic secretion beginning at a dose of 4 pmol/kg/min. The maximal effect was seen with 64 pmol/kg/min. We have detected, therefore, a new peptide, xenin 25, in human gastric mucosa; we have provided evidence for the presence of this peptide in the human circulation, and have shown a rise of plasma xenin concentrations after a meal. This peptide stimulates exocrine pancreatic secretion. Its physiologic role deserves further investigation.     

Interaction of xenin with the neurotensin receptor of guinea pig enteral smooth muscles

Xenin, a 25 amino acid peptide, interacts with the neurotensin receptor subtype 1 of intestinal muscles of the guinea pig. Replacement of the C-terminal Lys-Arg peptide bond in xenin 6 by a reduced pseudo-peptide bond augmented binding affinity to isolated jejunal and colonic muscle membranes by factors of 7.7 and 21.0 respectively; the potency to contract the jejunum and to relax the colon was increased by factors of 3.2 and 1.3. The C-terminus Trp-Ile-Leu (WIL) of xenin, in contrast to the C-terminus Tyr-Ile-Leu (YIL) of neurotensin, bound competitively to the muscle membranes. WIL blocked the contractile action of xenin in the jejunum and was synergistic with the relaxing action in the colon. The Lys-Arg motif and Trp in the C-terminus of xenin are essential structures in the action of xenin on the enteral smooth muscle receptors.     

Interaction of xenin with the neurotensin receptor of guinea pig enteral smooth muscles

Xenin, a 25 aminoacid peptide, interacts with the neurotensin receptor subtype 1 of intestinal muscles of the guinea pig. Replacement of the C-terminal Lys -Arg peptide bond in xenin 6 by a reduced pseudo-peptide bond augmented binding affinity to isolated jejunal and colonic muscle membranes by factors of 7.7 and 21.0 respectively; the potency to contract the jejunum and to relax the colon was increased by factors of 3.2 and 1.3. The C-terminus Trp-Ile-Leu (WIL) of xenin, in contrast to the C-terminus Tyr-Ile-Leu (YIL) of neurotensin, bound competitively to the muscle membranes. WIL blocked the contractile action of xenin in the jejunum and was synergistic with the relaxing action in the colon. The Lys -Arg motif and Trp in the C-terminus of xenin are essential structures in the action of xenin on the enteral smooth muscle receptors.     

Evidence for non-neurotensin receptor-mediated effects of xenin (1-25)--focus on intestinal microcirculation

Xenin (1-25) has been detected in various locations in mammalians. It has structural similarities with neurotensin and its intestinal effects are claimed to be mediated by neurotensin receptors. It has been shown to influence gastrointestinal motility. The effects of xenin (1-25) on intestinal microvascular perfusion after ischemia/reperfusion have not been investigated yet. Therefore, the superior mesenteric artery was clamped for 40 min in Wistar rats (n=8). Ten minutes prior to reperfusion, intravenous infusion of xenin (1-25) (5 nmol/kg/h) was started. By means of intravital microscopy, microvascular perfusion in the mucosal layer was assessed. Animals (n=8) with and without clamping of the superior mesenteric artery and infusion of the carrier solution served as controls.After ischemia/reperfusion, xenin (1-25) increased the density of perfused microvessels and the capillary red blood cell velocity compared to ischemic controls. Capillary red blood cell velocity was elevated (p<0.05). Xenin (1-25) improved the heterogeneous distribution of mucosal blood flow during reperfusion demonstrated by an increase of both the perfusion index and the percentage of perfused microvessels.We conclude that the effects of xenin (1-25) on intestinal microcirculation are significantly different from those previously described for neurotensin. A more complex effector mechanism must be postulated that may involve other regulatory peptides and receptors.     

Metabolism and potency of xenin and of its reduced hexapseudopeptide psi fragment in the dog

Xenin is a 25 amino acid peptide hormone, secreted into the circulation by specific endocrine cells in the duodenal mucosa. Plasma concentrations are elevated after sham feeding and feeding. In the present study the metabolism of xenin and of a C-terminal fragment was investigated. Xenin, its C-terminal hexapeptide, and a pseudopeptide analog psi (CH2NH) hexapeptide in which a psi reduced bond is introduced in the biologically important dibasic motif of the C-terminus were infused or injected intravenously in 14 anaesthetized dogs. Plasma disappearance time, metabolic clearance rate, the generation of metabolites, and biological effects on exocrine pancreatic secretion were determined employing radioimmunoassay, high pressure liquid chromatography, mass spectrometry (MALDI-MS), and sequence analysis. Half time after steady state infusion of xenin was 3.1 min(-1), that of psi xenin 6 was 6.2(-1) (p<0.01) Plasma concentrations of psi xenin 6 were significantly elevated (p<0.01), pancreatic secretion of volume was augmented by a factor of 50, and output of protein by a factor of 30 compared to unmodified xenin 6. MALDI-MS and sequencing after infusion of xenin revealed a C-terminal octapeptide fragment as primary metabolite. Introduction of a reduced pseudobond in the dibasic motif of xenin dramatically enhances biological potency. This indicates that such a reduced pseudopeptide may be useful in the treatment of bowel paralysis.     

Localization of xenin-immunoreactive cells in the duodenal mucosa of humans and various mammals.

Xenin is a 25-amino-acid peptide extractable from mammalian tissue. This peptide is biologically active. It stimulates exocrine pancreatic secretion and intestinal motility and inhibits gastric secretion of acid and food intake. Xenin circulates in the human plasma after meals. In this study, the cellular origin of xenin in the gastro-entero-pancreatic system of humans, Rhesus monkeys, and dogs was investigated by immunohistochemistry and immunoelectron microscopy. Sequence-specific antibodies against xenin detected specific endocrine cells in the duodenal and jejunal mucosa of all three species. These xenin-immunoreactive cells were distinct from enterochromaffin, somatostatin, motilin, cholecystokinin, neurotensin, and secretin cells, and comprised 8.8% of the chromogranin A-positive cells in the dog duodenum and 4.6% of the chromogranin A-positive cells in human duodenum. In all three species, co-localization of xenin was found with a subpopulation of gastric inhibitory polypeptide (GIP)-immunoreactive cells. Immunoelectron microscopy in the canine duodenal mucosa demonstrated accumulation of gold particles in round, homogeneous, and osmiophilic secretory granules with a closely adhering membrane of 187 +/- 19 nm diameter (mean +/- SEM). This cell type was found to be identical to the previously described canine GIP cell. Immunocytochemical expression of the peptide xenin in a subpopulation of chromogranin A-positive cells as well as the localization of xenin immunoreactivity in ultrastructurally characterized secretory granules permitted the identification of a novel endocrine cell type as the cellular source of circulating xenin.     

Peripheral and Central Administration of Xenin and Neurotensin Suppress Food Intake in Rodents

Xenin is a 25‐amino acid peptide highly homologous to neurotensin. Xenin and neurotensin are reported to have similar biological effects. Both reduce food intake when administered centrally to fasted rats. We aimed to clarify and compare the effects of these peptides on food intake and behavior. We confirm that intracerebroventricular (ICV) administration of xenin or neurotensin reduces food intake in fasted rats, and demonstrate that both reduce food intake in satiated rats during the dark phase. Xenin reduced food intake more potently than neurotensin following ICV administration. ICV injection of either peptide in the dark phase increased resting behavior. Xenin and neurotensin stimulated the release of corticotrophin‐releasing hormone (CRH) from ex vivo hypothalamic explants, and administration of α‐helical CRH attenuated their effects on food intake. Intraperitoneal (IP) administration of xenin or neurotensin acutely reduced food intake in fasted mice and ad libitum fed mice in the dark phase. However, chronic continuous or twice daily peripheral administration of xenin or neurotensin to mice had no significant effect on daily food intake or body weight. These studies confirm that ICV xenin or neurotensin can acutely reduce food intake and demonstrate that peripheral administration of xenin and neurotensin also reduces food intake. This may be partly mediated by changes in hypothalamic CRH release. The lack of chronic effects on body weight observed in our experiments suggests that xenin and neurotensin are unlikely to be useful as obesity therapies.     

A novel chemically modified analogue of xenin-25 exhibits improved glucose-lowering and insulin-releasing properties

Background: Xenin-25 is a K-cell derived gut peptide with insulin-releasing activity which is rapidly degraded following release into the circulation. We hypothesized that substitution of all naturally-occurring Lys and Arg residues with Gln would lead to prolonged enzyme resistance and enhanced biological efficacy.Methods: Peptide stability was assessed using murine plasma, in vitro insulin-releasing actions evaluated in BRIN-BD11 cells and acute glucose-lowering and insulin-releasing actions examined in high fat fed mice. For sub-chronic studies, a range of metabolic parameters and pancreatic histology were assessed in high fat fed mice which had received saline vehicle or xenin-25(gln) twice-daily for 21 days.Results: In contrast to native xenin-25, xenin-25(gln) was resistant to plasma-mediated degradation and significantly stimulated insulin secretion in BRIN-BD11 cells. Acute administration of xenin-25(gln) in high fat fed mice significantly reduced blood glucose and increased plasma insulin concentrations. Twice-daily administration of xenin-25(gln) in high fat fed mice did not affect food intake, body weight or circulating insulin concentrations but significantly decreased blood glucose from day 9 onwards. Furthermore, glucose tolerance, glucose-mediated insulin secretion, insulin sensitivity and GIP-stimulated insulin-release were significantly enhanced in xenin-25(gln)-treated mice. Pancreatic immunohistochemistry revealed decreased alpha cell area with increased beta cell area and beta-to-alpha cell ratio in xenin-25(gln)-treated mice. In addition, xenin-25(gln) exerted similar beneficial actions in ob/ob mice as demonstrated by reduced blood glucose, superior glycaemic response and glucose-mediated insulin release.Conclusions: Xenin-25(gln) is resistant to plasma-mediated degradation and exerts sustained and beneficial metabolic actions in high fat fed and ob/ob mice.General significance: Glutamine (gln)-modified analogues of xenin may represent an attractive therapeutic approach for type 2 diabetes.     

Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin

Xenin is a peptide that is co-secreted with the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response to feeding. Studies demonstrate that xenin has appetite suppressive effects and modulates glucose-induced insulin secretion. The present study was undertaken to determine the bioactivity and antidiabetic properties of two C-terminal fragment xenin peptides, namely xenin 18–25 and xenin 18–25 Gln. In BRIN-BD11 cells, both xenin fragment peptides concentration-dependently stimulated insulin secretion, with similar efficacy as the parent peptide. Neither fragment peptide had any effect on acute feeding behaviour at elevated doses of 500 nmol/kg bw. When administered together with glucose to normal mice at 25 nmol/kg bw, the overall insulin secretory effect was significantly enhanced in both xenin 18–25 and xenin 18–25 Gln treated mice, with better moderation of blood glucose levels. Twice daily administration of xenin 18–25 or xenin 18–25 Gln for 21 days in high fat fed mice did not affect energy intake, body weight, circulating blood glucose or body fat stores. However, circulating plasma insulin concentrations had a tendency to be elevated, particularly in xenin 18–25 Gln mice. Both treatment regimens significantly improved insulin sensitivity by the end of the treatment period. In addition, sustained treatment with xenin 18–25 Gln significantly reduced the overall glycaemic excursion and augmented the insulinotropic response to an exogenous glucose challenge on day 21. In harmony with this, GIP-mediated glucose-lowering and insulin-releasing effects were substantially improved by twice daily xenin 18–25 Gln treatment. Overall, these data provide evidence that C-terminal octapeptide fragments of xenin, such as xenin 18–25 Gln, have potential therapeutic utility for type 2 diabetes.     

Action of neurotensin on size, composition, and growth of pancreas and stomach in the rat

Since the gastrointestinal peptide neurotensin has a stimulatory effect on the secretion of the exocrine pancreas and an inhibitory effect on secretion and motility of the stomach, we investigated whether chronic parenteral administration of neurotensin would affect pancreatic and gastric growth. We therefore infused synthetic neurotensin subcutaneously (dose, 43 and 282 pmol X kg-1 X min-1) in 20 Wistar rats for 2 weeks using Alzet osmotic minipumps and compared pancreatic weight, DNA, RNA, protein, lipase, amylase, pancreatic polypeptide and insulin with these parameters in 10 control rats from the same litter with subcutaneously implanted plastic cylinders approximately the size of the minipumps. In another experiment, synthetic neurotensin (836 pmol X kg-1) was injected intraperitoneally three times a day for 3 days in 12 rats. Thereafter, we measured pancreatic DNA and in vitro incorporation of [3H]thymidine into pancreatic DNA. These effects were compared with the actions of caerulein and normal saline. Long term infusion of the high neurotensin dose induced an increase of pancreatic weight (control: 0.87 g, neurotensin: 1.02 g) and of DNA (control: 2.5 micrograms; neurotensin: 3.5 micrograms) and pancreatic polypeptide (control: 2.4 ng; neurotensin: 7.4 ng) contents, whereas pancreatic protein, RNA, amylase and lipase contents were not stimulated. In relation to DNA, these parameters even were significantly depressed. Insulin remained unchanged. Intraperitoneal injection of neurotensin induced an increase of pancreatic DNA content and stimulated [3H]thymidine incorporation into DNA (control: 11 000 dpm/g; neurotensin: 15 800 dpm/g pancreas). Moreover, long-term neurotensin infusion with the high dose led to a rise in protein concentration and an increase in the thickness of the gastric antrum; antral DNA concentration was insignificantly stimulated. Parenteral neurotensin in the doses and at the times administered, led therefore, to hyperplasia of the pancreas and induced growth of the gastric antrum. It is concluded that neurotensin can act as a trophic factor on pancreas and gastric antrum of the rat. It remains to be determined whether this represents a physiological effect of neurotensin.     

Neurotensin interacts with carbachol, secretin, and caerulein in the stimulation of the exocrine pancreas of the rat in vitro

In the present investigation the effect of neurotensin on pancreatic secretion of isolated pancreatic lobules from the rat was examined. We found a dose- and time-dependent stimulation of amylase release beginning with a concentration of 10(-9) M neurotensin. This response was potentiated by the cholinergic agonist carbachol, the gastrointestinal peptide secretin, and the CCK analogue caerulein. As we found neurotensin-immunoreactive nerves within the pancreas and as neurotensin-like immunoreactivity is present in the circulation (found previously), neurotensin may well be a further peptide taking part in the regulation of exocrine pancreatic secretion either as a hormone or a neurotransmitter. Neurotensin would then cooperate with cholinergic mechanisms, secretin, and CCK.     

A novel neurotensin/xenin fusion peptide enhances β-cell function and exhibits antidiabetic efficacy in high-fat fed mice

Neurotensin and xenin possess antidiabetic potential, mediated in part through augmentation of incretin hormone, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), action. In the present study, fragment peptides of neurotensin and xenin, acetyl-neurotensin and xenin-8-Gln, were fused together to create Ac-NT/XN-8-Gln. Following assessment of enzymatic stability, effects of Ac-NT/XN-8-Gln on in vitro β-cell function were studied. Subchronic antidiabetic efficacy of Ac-NT/XN-8-Gln alone, and in combination with the clinically approved GLP-1 receptor agonist exendin-4, was assessed in high-fat fed (HFF) mice. Ac-NT/XN-8-Gln was highly resistant to plasma enzyme degradation and induced dose-dependent insulin-releasing actions (P<0.05 to P<0.01) in BRIN-BD11 β-cells and isolated mouse islets. Ac-NT/XN-8-Gln augmented (P<0.001) the insulinotropic actions of GIP, while possessing independent β-cell proliferative (P<0.001) and anti-apoptotic (P<0.01) actions. Twice daily treatment of HFF mice with Ac-NT/XN-8-Gln for 32 days improved glycaemic control and circulating insulin, with benefits significantly enhanced by combined exendin-4 treatment. This was reflected by reduced body fat mass (P<0.001), improved circulating lipid profile (P<0.01) and reduced HbA1c concentrations (P<0.01) in the combined treatment group. Following an oral glucose challenge, glucose levels were markedly decreased (P<0.05) only in combination treatment group and superior to exendin-4 alone, with similar observations made in response to glucose plus GIP injection. The combined treatment group also presented with improved insulin sensitivity, decreased pancreatic insulin content as well as increased islet and β-cell areas. These data reveal that Ac-NT/XN-8-Gln is a biologically active neurotensin/xenin fusion peptide that displays prominent antidiabetic efficacy when administered together with exendin-4.     

Hepatic bile and pancreatic exocrine secretions evoked by gastrointestinal peptides in sheep

The secretory response of hepatic bile and exocrine pancreas to gastrointestinal peptides has been studied in chronically cannulated sheep. Pancreatic juice flow and protein output were evoked dose dependently by intraportal injection of secretin, CCK-8, caerulein, VIP and neurotensin. However, biliary secretion was evoked by only secretin. Biliary and pancreatic exocrine secretions were enhanced by delivered gastric juice into the duodenum as followed by the increased plasma concentration of immunoreactive secretin (IRS). Results suggest that secretin is the major peptide that regulates pancreatic exocrine secretion and hepatic bile production in the sheep.     

Mechanisms regulating adrenomedullin gene expression in the left ventricle: role of mechanical load

Xenin is a 25 amino acid peptide produced by specific endocrine cells of the duodenal mucosa. Xenin has multiple biological actions in the gastrointestinal tract. It modulates intestinal motility, affects exocrine pancreatic secretion, and gastric secretion of acid. In the present investigation, we studied plasma concentration of xenin in volunteers after modified sham feeding and after meals of different composition. Plasma xenin concentrations were determined by radioimmunoassay in unextracted plasmas and after acidic extraction using C-18 Sep-Pak chromatography and after neutral extraction using affinity filtration. Both extraction methods were followed by C 18 r.p. HPLC chromatography. Xenin plasma concentrations in unextracted and in extracted plasma rose significantly after modified sham feeding when the food was brought to the volunteers from another room immediately before sham feeding started. When the volunteers had the opportunity to observe the preparation of the meal, xenin plasma concentrations during fasting were high and no further rise was observed after sham feeding. Isocaloric feeding resulted in elevated xenin concentrations in unextracted plasma and after high-pressure liquid chromatography. The methods of extraction, acidic or neutral, did not affect the results. CONCLUSION: Cephalic factors, investigated by modified sham feeding, stimulate release of xenin into the circulation. Xenin may participate in the central nervous regulation of gastrointestinal function.     

Neurotensin inhibition of gastric exocrine secretions in the cat

The gastric exocrine inhibitory activities of neurotensin were characterized in conscious cats prepared with gastric fistulae. Neurotensin was a potent inhibitor of pentagastrin-stimulated pepsin secretion (ID50, approx. 0.3 mumol . kg-1 . h-1) but was approximately 60 times less potent against acid secretion. Neurotensin did not significantly reduce submaximal histamine-stimulated acid or pepsin secretions. the total 2 h acid and pepsin outputs in response to insulin-hypoglycaemia were not reduced by neurotensin, although the peak 15-min outputs were reduced. The reduction in peak secretion was possibly related to neurotensin antagonism of the ability of insulin to lower blood glucose concentrations. Neurotensin alone was not hyperglycaemic when given as an intravenous infusion. Two C-terminal fragments of neurotensin, the dodecapeptide and nonapeptide, inhibited pentagastrin-stimulated pepsin secretion, but were less potent than neurotensin. The observations with the C-terminal fragments indicate that the major determinants of gastric exocrine inhibitory activity of neurotensin reside in its C-terminal; this agrees with observations on other biological activities of neurotensin. The reduced potency of the dodecapeptide indicates the importance of the N-terminal pyroglutamyl residue for full gastric exocrine inhibitory activity.     

Somatostatin action on insulin secretion induced by chicken and porcine vasoactive intestinal peptide in the perfused rat pancreas

The isolated perfused rat pancreas with duodenal exclusion was used to study the stimulation of glucose-induced insulin release in response to chicken and porcine vasoactive intestinal peptide (VIP). The insulin response to 5.5 or 16.7 mM glucose was markedly enhanced by 750 pM porcine VIP and a concentration of 250 pM was still effective. At 250 pM, chicken VIp exhibited a slightly higher potency than porcine VIP at both glucose concentrations. The main difference between the two peptides was that the effect of porcine VIP disappeared immediately after the peptide suppression but tha of chicken VIP persisted for an additional period of 8-10 min. Somatostatin (10 ng/ml) blocked the stimulatory effect of both VIP molecules on glucose-induced insulin secretion. After suppression of VIP and somatostatin from the perfusion medium, insulin release increased to levels higher than those with glucose alone in the case of the avian peptide, but not in that porcine VIP. The data are consistent with previous results in the literature on stimulation of exocrine pancreas secretion and interaction with intestinal epithelium.     

Effect of acetylcholine and new cholinergic derivative on amylase output, insulin, glucagon, and somatostatin secretions from perfused isolated rat pancreas

The effect of infused acetylcholine and (2-acetyllactoyloxyethyl)-trimethylammonium hemi-1,5-naphthalenedisulfonate (aclatonium napadisilate), a new cholinergic drug . On endocrine and exocrine secretory responses was simultaneously investigated during the perfusion of isolated rat pancreases. Acetylcholine (1.1 microM) stimulated the output of pancreatic juice and amylase, and significantly elicited the production of both insulin and glucagon. Its effect on somatostatin secretion, however, was minimal. Both pancreatic juice flow and amylase output were also significantly stimulated by aclatonium napadisilate (12 microM). These stimulatory effects of aclatonium napadisilate on the exocrine pancreas were blocked by atropine (25 microM). Aclatonium napadisilate could stimulate glucagon, but could not influence insulin and somatostatin secretion. The addition of atropine had no effect on the release of insulin, glucagon, and somatostatin. These results indicate that the effects of aclatonium napadisilate is cholinergic, and that the action is muscarinic. In addition, it can be concluded that pancreatic somatostatin secretion, as well as other hormones from islet cells, is controlled by the parasympathetic nervous system.     

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.