Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas

1994 ◽  
Vol 267 (2) ◽  
pp. G207-G212 ◽  
Author(s):  
K. Y. Lee ◽  
Y. L. Lee ◽  
C. D. Kim ◽  
T. M. Chang ◽  
W. Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Exocrine Secretion ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Pancreatic Exocrine Secretion ◽  
Arterial Infusion ◽  
Perfused Rat Pancreas ◽  
Pancreatic Exocrine ◽  
Protein Output

In conscious rats, we have previously shown that immunoneutralization of circulating insulin with a rabbit anti-insulin serum abolished the pancreatic exocrine secretion stimulated by a meal or a combination of exogenous secretin and cholecystokinin octapeptide (CCK-8). To investigate the mechanism of endogenous insulin action on the exocrine pancreas, isolated rat pancreata were perfused with intra-arterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 ml/min, whereas both pancreatic juice and portal venous effluent were collected separately in 15-min samples. Simultaneous intra-arterial infusion of secretin and CCK-8 in doses of 0.75 and 4.2 pmol/h; respectively, significantly increased volume, bicarbonate, and protein output in 7 rat pancreata (P < 0.01). When a rabbit anti-insulin serum was administered intra-arterially (0.1-ml bolus followed by 0.1 ml for 10 min), pancreatic secretion of volume, bicarbonate, and protein output was profoundly suppressed (n = 7, P < 0.01), whereas a normal rabbit serum failed to influence pancreatic secretion. The decrease in pancreatic secretion by the antiserum coincided with a significant increase in somatostatin in portal venous effluent from 1.4 +/- 0.2 to 4.1 +/- 0.8 pM (n = 6, P < 0.05). The combined administration of a rabbit antisomatostatin serum (0.4 ml) and the anti-insulin serum partially reversed the effect of the anti-insulin serum alone. Thus the pancreatic secretion was significantly greater than that achieved by the anti-insulin serum alone (P < 0.05). These observations strongly suggest that the action of insulin on exocrine pancreas is mediated by its local or paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals MEK inhibits secretin release and pancreatic secretion: roles of secretin-releasing peptide and somatostatin

2001 ◽  
Vol 280 (5) ◽  
pp. G890-G896 ◽  
Author(s):  
James P. Li ◽  
Kae Yol Lee ◽  
Ta-Min Chang ◽  
William Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Pancreatic Exocrine ◽  
Small Intestinal ◽  
Secretin Release

We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.

Neurohormonal mechanism of pancreatic exocrine secretion stimulated by sodium oleate and L-tryptophan in dogs

1992 ◽  
Vol 263 (1) ◽  
pp. G12-G16 ◽  
Author(s):  
Y. H. Jo ◽  
Y. L. Lee ◽  
K. Y. Lee ◽  
T. M. Chang ◽  
W. Y. Chey
Keyword(s):  
Pancreatic Juice ◽  
Sodium Oleate ◽  
Pancreatic Secretion ◽  
Exocrine Secretion ◽  
Dependent Manner ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Exocrine ◽  
Protein Output ◽  
Dose Dependent ◽  
Cck Release

In the present investigation, we have studied the effect of atropine on the pancreatic secretion stimulated by intraduodenal administration of either sodium oleate or exogenous cholecystokinin (CCK). In four dogs prepared with gastric and Thomas duodenal cannulas, pancreatic juice was collected for measurement of volume, bicarbonate, and protein output, and peripheral venous blood samples were obtained for radioimmunoassay of both secretin and CCK. Volume, bicarbonate, and protein output of the pancreatic juice increased significantly in response to sodium oleate (1-4 mmol/h) in a dose-dependent manner. The increase in pancreatic secretion paralleled the increments in both plasma CCK and secretin. Atropine given intravenously suppressed completely both pancreatic secretion and release of CCK stimulated by sodium oleate, whereas the release of secretin was not affected. Pancreatic secretion was significantly increased in a dose-dependent manner by exogenous CCK octapeptide (CCK-8) at 16, 32, and 64 micrograms (14, 28, and 56 pmol).kg-1.h-1. Atropine inhibited protein output only partially, but it did not influence bicarbonate output. In five additional dogs, the effect of atropine on L-tryptophan-stimulated pancreatic secretion was studied. Interestingly, atropine failed to influence the CCK release and pancreatic secretion of volume and bicarbonate, except for protein secretion, which was significantly inhibited. It was shown previously that atropine inhibited significantly the pancreatic secretion of bicarbonate stimulated by secretin in physiological doses. Thus we conclude that the inhibition by atropine of the pancreatic exocrine secretion stimulated by sodium oleate is mediated by both suppression of CCK release and inhibition of action of secretin on the exocrine pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Significant cholinergic role in secretin-stimulated exocrine secretion in isolated rat pancreas

1998 ◽  
Vol 274 (2) ◽  
pp. G413-G418 ◽  
Author(s):  
Hyung Seo Park ◽  
Yun Lyul Lee ◽  
Hyeok Yil Kwon ◽  
William Y. Chey ◽  
Hyoung Jin Park
Keyword(s):  
Pancreatic Secretion ◽  
Cholinergic Neurons ◽  
Electrical Field Stimulation ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Cholinergic Tone ◽  
Pancreatic Exocrine ◽  
Two Parameters

Effects of intrapancreatic cholinergic activation by electrical field stimulation (EFS) on secretin-stimulated pancreatic exocrine secretion were investigated in the totally isolated perfused rat pancreas. EFS at 15 V, 2 ms, and 8 Hz for 45 min markedly increased spontaneous pancreatic secretion. This increase was completely inhibited by tetrodotoxin (1 μM) but not by hexamethonium (100 μM). Atropine (2 μM) significantly reduced the EFS-evoked volume flow and amylase output by 52% and 80%, respectively. EFS further increased the secretin (12 pM)-stimulated pancreatic secretion of fluid and amylase. The increases of the two parameters were significantly suppressed by atropine by 28% and 72%, respectively. Interestingly, EFS significantly increased concentrations of somatostatin-like immunoreactivity in portal venous effluents. When pertussis toxin (200 ng/ml) or rabbit antisomatostatin serum (0.1 ml/10 ml; titer of 1:50,000) was intra-arterially administered, EFS further increased the secretin-stimulated pancreatic secretion. In conclusion, the activation of intrapancreatic cholinergic neurons potentiated the secretin action on pancreatic exocrine secretion in the rat. This potentiating effect was significantly reduced by local somatostatin released during EFS that activated intrapancreatic cholinergic tone.

scholarly journals Age-associated changes in pancreatic exocrine secretion of the isolated perfused rat pancreas

2013 ◽  
Vol 29 (1) ◽  
pp. 19 ◽  
Author(s):  
Zheng-er Jiang ◽  
ChengZhe Jiang ◽  
Baihui Chen ◽  
Chin Su Koh ◽  
Jun-Hwan Yong ◽  
...  
Keyword(s):  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Isolated Perfused Rat Pancreas ◽  
Pancreatic Exocrine

Microinjection of TRH analogue into the dorsal vagal complex stimulates pancreatic secretion in rats

1995 ◽  
Vol 269 (3) ◽  
pp. G328-G334 ◽  
Author(s):  
T. Okumura ◽  
I. L. Taylor ◽  
T. N. Pappas
Keyword(s):  
Vagus Nerve ◽  
Pancreatic Secretion ◽  
Exocrine Secretion ◽  
Dependent Manner ◽  
Dorsal Vagal Complex ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Neurophysiological Studies ◽  
Pancreatic Exocrine ◽  
The Brain

Thyrotropin-releasing hormone (TRH) stimulates pancreatic exocrine secretion through the vagus nerve when injected into rat cerebrospinal fluid. However, little is known about the exact site of action of TRH in the brain to stimulate pancreatic secretion. Recent neuroimmunochemical and neurophysiological studies suggest that TRH could be a neurotransmitter in the dorsal vagal complex, which sends fibers to the pancreas through the vagus nerve. We therefore hypothesized that TRH may act centrally in the dorsal vagal complex to stimulate pancreatic exocrine secretion. To address this question, a TRH analogue, [1-methyl-(S)-4,5-dihydroorotyl]-L-histidyl-L-prolinamide- NH2, was microinjected into the dorsal vagal complex, and basal pancreatic fluid flow and protein secretion were measured in urethan-anesthetized rats. Microinjection of TRH analogue (0.2-2 ng/site) into the dorsal vagal complex significantly stimulated pancreatic flow and protein output in a dose-dependent manner. As a control, microinjection of the TRH analogue into the brain stem outside the vagal complex failed to stimulate pancreatic secretion. Either bilateral subdiaphragmatic vagotomy or atropine abolished the ability of the TRH analogue to stimulate pancreatic secretion. Our data suggest that TRH acts in the dorsal vagal complex to stimulate pancreatic secretion through vagus-dependent and cholinergic pathways. The dorsal vagal complex may play an important role as a central site for control of the exocrine pancreas.

Effect of [(CH2NH)4,5]secretin on pancreatic exocrine secretion in guinea pigs and rats

1993 ◽  
Vol 265 (5) ◽  
pp. G805-G810 ◽  
Author(s):  
C. D. Kim ◽  
P. Li ◽  
K. Y. Lee ◽  
D. H. Coy ◽  
W. Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Guinea Pigs ◽  
Partial Agonist ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Acini ◽  
Secretin Receptor ◽  
Pancreatic Exocrine

[psi 4,5]Secretin was shown to be a secretin receptor antagonist that inhibits secretin-stimulated increase in adenosine 3',5'-cyclic monophosphate in isolated pancreatic acini of the guinea pig. To determine whether it inhibits pancreatic exocrine secretion in vivo, we have studied the effect of [psi 4,5]secretin on the pancreatic secretion stimulated by secretin in anesthetized guinea pigs and rats. In basal state, [psi 4,5]secretin given intravenously for 2 or 3 h in varying doses of 1.6-32.7 nmol.kg-1.h-1 dose dependently increased pancreatic secretion of both fluid and bicarbonate during the 1st h, but it returned gradually to basal level within 2 or 3 h. On the other hand, [psi 4,5]secretin significantly inhibited the pancreatic secretion stimulated by either exogenous or endogenous secretin in a dose-related manner. The inhibitory effect of [psi 4,5]secretin in guinea pigs was greater than that in rats. However, it did not completely block the secretin-stimulated pancreatic secretion, whereas a rabbit antisecretin serum suppressed it completely. We conclude that 1) in the unstimulated state, [psi 4,5]secretin is a partial agonist of pancreatic exocrine secretion of both fluid and bicarbonate; and 2) when pancreatic secretion is stimulated by secretin, unlike an antisecretin serum, it is a partial inhibitor in intact guinea pigs and rats.

Effect of ACh and calmodulin inhibitor on O2 transfer from exocrine pancreatic microvessels of rats

1996 ◽  
Vol 271 (1) ◽  
pp. H1-H7 ◽  
Author(s):  
A. Seiyama ◽  
H. Kosaka ◽  
T. Shiga
Keyword(s):  
Pancreatic Secretion ◽  
Binding Protein ◽  
Control Level ◽  
Exocrine Secretion ◽  
The Other ◽  
Pancreatic Exocrine Secretion ◽  
O2 Extraction ◽  
Pancreatic Exocrine ◽  
O2 Transfer ◽  
Krebs Henseleit Buffer

Effects of acetylcholine (ACh) and calmodulin (CaM) inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), on the rate of O2 release (Ro2) from single exocrine pancreatic microvessels of anesthetized rats were investigated with dual-spot microspectroscopy. The surface of the pancreas was superfused with Krebs-Henseleit buffer containing various concentrations of ACh and/or W-7. Superfusion of ACh (> or = 20 microM) elevated Ro2 as well as pancreatic secretion approximately 2.5 times higher than that of control level, whereas superfusion of W-7 (> or = 100 microM) reduced approximately 50%. In both cases, O2 inflow in single microvessels, as quantified by oxyhemoglobin inflow into the microvessels, was maintained at control level. On the other hand, superfusion of both ACh and W-7 did not modify Ro2 and pancreatic secretion, despite significant reduction in O2 inflow. These results indicate that 1) the ACh-induced elevation of O2 release from single microvessels is accomplished by increased O2 extraction instead of increased O2 inflow in the microvessels, and 2) the activity of a W-7-sensitive Ca2+ binding protein, most likely CaM, is responsible for half of the microvascular O2 transfer and of the pancreatic exocrine secretion.

Inhibitory effect of central dopamine on basal pancreatic secretion in conscious rats

1998 ◽  
Vol 274 (1) ◽  
pp. G29-G34 ◽  
Author(s):  
Masao Masuda ◽  
Setsuko Kanai ◽  
Kyoko Miyasaka
Keyword(s):  
Pancreatic Secretion ◽  
Sch 23390 ◽  
Sympathetic Nerves ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
External Jugular Vein ◽  
Pancreatic Exocrine Secretion ◽  
Conscious Rats ◽  
Brain Ventricle ◽  
Pancreatic Exocrine

We examined the role and the peripheral mechanism of action of central dopamine on basal pancreatic exocrine secretion in conscious rats. Rats were fitted with bile and pancreatic catheters to collect bile and pancreatic juice separately and also with a left lateral brain ventricle and external jugular vein catheters. After 90-min basal collection, the D1- and D2-receptor antagonists (Sch-23390 and eticlopride, respectively) and dopamine were administered into the lateral brain ventricle. Sch-23390 (30, 100, and 300 nmol/rat), but not eticlopride (300 nmol/rat), stimulated pancreatic fluid and protein secretion. Dopamine (30, 100, and 300 nmol/rat) inhibited pancreatic secretion dose dependently. Pretreatment with Sch-23390 prevented the inhibitory effect of dopamine. Intravenously injected Sch-23390 or dopamine had no effect on pancreatic secretion. The inhibitory effect of dopamine was blocked by bretylium, an inhibitor of norepinephrine release, and phentolamine, an α-blocker, but not by vagotomy. The β-antagonist propranolol alone significantly inhibited basal pancreatic secretion, and dopamine did not modify the inhibitory effect of propranolol. The proton pump inhibitor omeprazole partially but not completely reduced the inhibition by dopamine. These results suggest that central dopamine inhibits pancreatic exocrine secretion via D1-like receptors and that the inhibitory effect is mediated via sympathetic nerves, especially α-adrenoceptors.

scholarly journals Effects of γ-aminobutyric acid on secretagogue-induced exocrine secretion of isolated, perfused rat pancreas

2000 ◽  
Vol 279 (4) ◽  
pp. G677-G682 ◽  
Author(s):  
Hyung Seo Park ◽  
Hyoung Jin Park
Keyword(s):  
Receptor Antagonist ◽  
Electrical Field Stimulation ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Electrical Field ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Isolated Perfused Rat Pancreas ◽  
Pancreatic Exocrine ◽  
Somatostatin Antagonist

Because GABA and its related enzymes have been determined in β-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated, perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30, and 100 μM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated CCK (10 pM)-, gastrin-releasing peptide (100 pM)-, or electrical field stimulation-induced pancreatic secretions of fluid and amylase dose dependently. The GABA (30 μM)-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 μM), a GABAA receptor antagonist, but were not affected by saclofen (10 μM), a GABAB receptor antagonist. The enhancing effects of GABA (30 μM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 μM) but were partially reduced by cyclo-(7-aminoheptanonyl-Phe-d-Trp-Lys-Thr[BZL]) (10 nM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which predominantly induce enzyme secretion, via GABAA receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release.

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