Effects of neuromedin B and neuromedin C on exocrine and endocrine rat pancreas

1987 ◽  
Vol 252 (4) ◽  
pp. G491-G498 ◽  
Author(s):  
M. Otsuki ◽  
M. Fujii ◽  
T. Nakamura ◽  
S. Tani ◽  
T. Oka ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Exocrine Secretion ◽  
Exocrine Pancreatic Function ◽  
Isolated Perfused Pancreas ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Neuromedin B ◽  
Pancreatic Exocrine ◽  
Stimulate Insulin Release

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa and show striking sequence homology with bombesin and gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin B and C on exocrine pancreatic function and insulin release have been compared with bombesin and GRP-27 in isolated pancreatic acini and isolated perfused pancreas in rat. Neuromedin B and C as well as bombesin and GRP-27 were able to cause stimulation of amylase release. The relative efficacy of neuromedin B, C, bombesin, and GRP-27 was the same as that of cholecystokinin octapeptide (CCK-8). Bombesin and GRP-27 were equipotent, and both were approximately 15-fold less potent than CCK-8. Neuromedin C was approximately 2-fold more potent, whereas neuromedin B as approximately 10-fold less potent than bombesin and GRP-27. All of these peptides stimulated insulin release that was limited to the first 3 min of a 20-min perfusion. However, GRP-27 and its related peptides were weak stimulants of insulin release compared with their abilities to stimulate exocrine pancreatic secretion. Bombesin and neuromedin B id not stimulate insulin release at doses stimulating pancreatic exocrine secretion. Neuromedin B was also approximately 10-fold less potent than neuromedin C, bombesin, and GRP-27 in eliciting insulin secretion. Because bombesin-like immunoreactivity is found to be present in nerves in the pancreas, neuromedin B and C may be neurotransmitters or neuromodulators and exert a direct local neurocrine action on enzyme secretion by acinar cells and insulin secretion by the islets.

Action of cholecystokinin analogues on exocrine and endocrine rat pancreas

1986 ◽  
Vol 250 (4) ◽  
pp. G405-G411
Author(s):  
M. Otsuki ◽  
Y. Okabayashi ◽  
A. Ohki ◽  
T. Oka ◽  
M. Fujii ◽  
...  
Keyword(s):  
Amino Acid ◽  
Insulin Release ◽  
Pancreatic Enzyme ◽  
Exocrine Secretion ◽  
Amino Acid Residues ◽  
Isolated Perfused Pancreas ◽  
Pancreatic Acini ◽  
Rat Pancreas ◽  
Pancreatic Exocrine ◽  
Stimulation Of

In the present study we have examined the abilities of cholecystokinin-(26-33)-amide [CCK-(26-33)-NH2, CCK-8], nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(30-33)-NH2 (CCK-4), CCK-(26-33)-OH (deamidated CCK-8), and succinyl CCK-(27-31)-NH2 (Suc-Des-Asp6,Phe7-CCK-7) to stimulate exocrine pancreatic secretion from both isolated pancreatic acini and isolated perfused pancreas. We have also compared this action with their ability to cause insulin release. The modification of either the N- or C-terminal amino acid residues of CCK-8 decreased in potency, but the magnitude of the stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same. The minimal effective concentration of CCK-8, desulfated CCK-8, and CCK-4 for insulin release from the isolated rat pancreas in the presence of 8.3 mM glucose was the same as that for pancreatic exocrine secretion. In contrast, the concentrations of deamidated CCK-8 and Suc-Des-Asp6,Phe7-CCK-7 required to produce insulin release were 5-10 times higher than those required to cause stimulation of pancreatic enzyme and juice secretion. It is concluded therefore that the N-terminal 4-amino acid residues or the C-terminal 2-amino acid residues of CCK-8 are not essential for biological activity but do contribute to its potency. In addition, the C-terminal 2-amino acid residues and an amide group in the C-terminal phenylalanine residue of CCK-8 appear to be important determinants of the insulin-releasing activity of the CCK peptides.

Structural requirements of peptide YY for biological activity at enteric sites

1992 ◽  
Vol 263 (5) ◽  
pp. G695-G701 ◽  
Author(s):  
K. Yoshinaga ◽  
T. Mochizuki ◽  
N. Yanaihara ◽  
K. Oshima ◽  
M. Izukura ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Insulin Release ◽  
Peptide Yy ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Structural Requirements ◽  
Pancreatic Exocrine

Peptide YY (PYY) is a colonic hormone consisting of 36 amino acids that is a potent inhibitor of pancreatic exocrine, gastric acid, and insulin secretion. The objective of the present experiments was to characterize the structural requirements of PYY for inhibition of pancreatic exocrine, gastric acid, and insulin secretion, using conscious dogs prepared with gastric and pancreatic fistulas. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (400 pmol.kg-1 x h-1) inhibited cholecystokinin-8-stimulated (25 pmol.kg-1 x h-1) pancreatic exocrine secretion (P < 0.05); however, PYY-(1-10), PYY-(1-20), PYY-(6-36), PYY-(10-36), PYY-(13-36), PYY-(24-36), and PYY-(27-36) did not inhibit pancreatic exocrine secretion. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (200, 400, 800 pmol.kg-1 x h-1) inhibited pentagastrin (0.5 microgram.kg-1 x h-1)-stimulated gastric acid secretion (P < 0.05), as well as 2-deoxy-D-glucose-stimulated insulin release (75 mg/kg) in a dose-related manner. PYY-(6-36), PYY-(13-36), and [Leu31, Pro34] neuropeptide Y did not inhibit either gastric acid secretion or insulin release. In the gastric acid and insulin secretion bioassays, PYY-(1-36) was significantly more potent than PYY-(3-36) and PYY-(4-36); however, in the pancreatic exocrine secretion bioassay, the inhibitory effects of PYY-(3-36) and PYY-(1-36) did not differ significantly. PYY-(4-36) was less potent than PYY-(1-36) on pancreatic exocrine secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Decapeptide of Mammalian Bombesin and Neuromedin B on Pancreatic Exocrine Secretion in the Rat

Digestion ◽  
1986 ◽  
Vol 34 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Mitsuyoshi Namba ◽  
Mohammad A. Ghatei ◽  
Margarita Ghiglione ◽  
Stephen R. Bloom
Keyword(s):  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Neuromedin B ◽  
Pancreatic Exocrine

Actions of Neuromedin-B and Neuromedin-C on Amylase Release from Isolated Rat Pancreatic Acini

Pancreas ◽  
1987 ◽  
Vol 2 (3) ◽  
pp. 252-257 ◽  
Author(s):  
Makoto Otsuki ◽  
Masatoshi Fuji ◽  
Takahiko Nakamura ◽  
Satoshi Tani ◽  
Toru Oka ◽  
...  
Keyword(s):  
Amylase Release ◽  
Pancreatic Acini ◽  
Neuromedin B ◽  
Isolated Rat

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.

Role of endogenous cholecystokinin on vagally stimulated pancreatic secretion in dogs

1989 ◽  
Vol 257 (6) ◽  
pp. G944-G949
Author(s):  
C. K. Kim ◽  
K. Y. Lee ◽  
T. Wang ◽  
G. Sun ◽  
T. M. Chang ◽  
...  
Keyword(s):  
Pancreatic Secretion ◽  
Plasma Concentrations ◽  
Exocrine Secretion ◽  
Vagus Nerves ◽  
Pancreatic Acini ◽  
Venous Circulation ◽  
Gut Hormone ◽  
Pancreatic Exocrine ◽  
Cck Receptor Antagonist

Pancreatic exocrine secretion was evoked by electrical stimulation of the vagus nerves (EVS) in dogs to determine whether a gut hormone was responsible for the pancreatic stimulatory activity. In 39 dogs, pancreatic juice was continuously collected to measure volume, bicarbonate, and amylase output, while portal and femoral venous plasma concentrations of gastrin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), and pancreatic polypeptide (PP) were determined by radioimmunoassay. EVS produced a significant increase in the pancreatic secretion. Although concentrations of all four peptides significantly increased in plasma, only CCK at the concentration in venous circulation was bioactive in dispersed rat pancreatic acini preparations. This bioactivity of CCK was completely blocked by CR 1409, a CCK-receptor antagonist. The pancreatic secretion by EVS was reduced significantly by intravenous MK-329 (formerly L364,718) to as low as 22% of control values and was completely suppressed by intravenous atropine. The increment in plasma CCK by EVS was also significantly suppressed by atropine. The present study indicates that increased pancreatic secretion by EVS is in part mediated by endogenous CCK.

Glibenclamide inhibits islet carnitine palmitoyltransferase 1 activity, leading to PKC-dependent insulin exocytosis

2003 ◽  
Vol 285 (2) ◽  
pp. E438-E446 ◽  
Author(s):  
Mikael Lehtihet ◽  
Nils Welsh ◽  
Per-Olof Berggren ◽  
George A. Cook ◽  
Åke Sjöholm
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Secretory Granules ◽  
Carnitine Palmitoyltransferase ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Insulin Exocytosis ◽  
Carnitine Palmitoyltransferase 1 ◽  
Stimulate Insulin Release

Hypoglycemic sulfonylureas such as glibenclamide have been widely used to treat type 2 diabetic patients for 40 yr, but controversy remains about their mode of action. The widely held view is that they promote rapid insulin exocytosis by binding to and blocking pancreatic β-cell ATP-dependent K+ (KATP) channels in the plasma membrane. This event stimulates Ca2+ influx and sets in motion the exocytotic release of insulin. However, recent reports show that >90% of glibenclamide-binding sites are localized intracellularly and that the drug can stimulate insulin release independently of changes in KATP channels and cytoplasmic free Ca2+. Also, glibenclamide specifically and progressively accumulates in islets in association with secretory granules and mitochondria and causes long-lasting insulin secretion. It has been proposed that nutrient insulin secretagogues stimulate insulin release by increasing formation of malonyl-CoA, which, by blocking carnitine palmitoyltransferase 1 (CPT-1), switches fatty acid (FA) catabolism to synthesis of PKC-activating lipids. We show that glibenclamide dose-dependently inhibits β-cell CPT-1 activity, consequently suppressing FA oxidation to the same extent as glucose in cultured fetal rat islets. This is associated with enhanced diacylglycerol (DAG) formation, PKC activation, and KATP-independent glibenclamide-stimulated insulin exocytosis. The fat oxidation inhibitor etomoxir stimulated KATP-independent insulin secretion to the same extent as glibenclamide, and the action of both drugs was not additive. We propose a mechanism in which inhibition of CPT-1 activity by glibenclamide switches β-cell FA metabolism to DAG synthesis and subsequent PKC-dependent and KATP-independent insulin exocytosis. We suggest that chronic CPT inhibition, through the progressive islet accumulation of glibenclamide, may explain the prolonged stimulation of insulin secretion in some diabetic patients even after drug removal that contributes to the sustained hypoglycemia of the sulfonylurea.

Secretory effects of VIP on isolated perfused porcine pancreas.

1978 ◽  
Vol 235 (4) ◽  
pp. E387 ◽  
Author(s):  
S L Jensen ◽  
J Fahrenkrug ◽  
J J Holst ◽  
O V Nielsen ◽  
O B Schaffalitzky de Muckadell
Keyword(s):  
Insulin Release ◽  
Glucose Concentration ◽  
Glucagon Secretion ◽  
Exocrine Secretion ◽  
Dependent Manner ◽  
Glucagon Release ◽  
Porcine Pancreas ◽  
Insulin And Glucagon Secretion ◽  
Pancreatic Exocrine ◽  
Dose Dependent

We studied the secretion of insulin, glucagon, and the exocrine secretion of the isolated perfused porcine pancreas in response to vasoactive intestinal polypeptide (VIP) in concentrations ranging from 30 to 18,750 pmol/liter at various concentrations of glucose in the perfusion medium. VIP stimulated the insulin and glucagon secretion in a dose-dependent manner. The response pattern was critically dependent on the glucose concentration. In the presence of a glucose concentration of 7.5 mmol/liter, VIP enhanced insulin release without affecting glucagon release. Maximal insulin release was obtained at a VIP concentration of 3,750 pmol/liter. At a glucose concentration of 5.0 or 3.5 mmol/liter, VIP enhanced glucagon release but not insulin release. VIP stimulated the exocrine secretion in a secretin-like manner. The lowest concentration of VIP observed to increase pancreatic exocrine secretion was 30 pmol/liter, whereas the maximal pancreatic exocrine responses were not obtained.

scholarly journals Insulin Secretion and Pancreatic Exocrine Secretion in the Aged

1976 ◽  
Vol 13 (1) ◽  
pp. 8-15
Author(s):  
Yoshito Shimizu ◽  
Kazuko Hiramatsu ◽  
Kanji Miyake ◽  
Yoshihisa Tomiyama ◽  
Masamichi Shimono ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Exocrine Secretion ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Exocrine
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