Motilin controls cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs

1998 ◽  
Vol 274 (1) ◽  
pp. G87-G95 ◽  
Author(s):  
Hideki Suzuki ◽  
Erito Mochiki ◽  
Norihiro Haga ◽  
Minoru Satoh ◽  
Akiyoshi Mizumoto ◽  
...  
Keyword(s):  
Insulin Release ◽  
Islet Cells ◽  
Contractile Activity ◽  
Close Association ◽  
Phase Iii ◽  
Force Transducers ◽  
Specific Radioimmunoassay ◽  
Plasma Motilin ◽  
Interdigestive Migrating Contractions ◽  
Perifusion System

The effect of motilin on insulin release has not been studied in the interdigestive state. Adult mongrel dogs were chronically implanted with force transducers in the stomach and duodenum to monitor contractile activity, and the plasma motilin and insulin concentrations were measured by a specific radioimmunoassay and enzyme immunoassay, respectively. The concentration of insulin in plasma was found to fluctuate in close association with that of motilin and phase III of the interdigestive migrating contractions in the stomach. This spontaneous release of insulin was mimicked by intravenous infusion of motilin at a dose of 0.3 μg ⋅ kg−1⋅ h−1. Exogenous motilin (0.01–0.3 μg/kg) dose dependently stimulated insulin release, which was abolished by atropine, hexamethonium, ondansetron, and truncal vagotomy. Phentolamine significantly enhanced, whereas propranolol inhibited, motilin-induced insulin release. In a perifusion system using islet cells from the canine pancreas, motilin did not affect insulin release. In conclusion, motilin stimulates insulin release through vagal cholinergic, muscarinic receptors on pancreatic β-cells, and the effect appears to be modulated by adrenergic nerves.

Regulation of plasma motilin by opioids in the dog

1989 ◽  
Vol 257 (1) ◽  
pp. G41-G45
Author(s):  
P. Poitras ◽  
M. Boivin ◽  
R. G. Lahaie ◽  
L. Trudel
Keyword(s):  
Opioid Receptor ◽  
Contractile Activity ◽  
Endogenous Opioids ◽  
Phase Iii ◽  
Endogenous Opiates ◽  
Small Intestinal Motility ◽  
Opioid Administration ◽  
Small Intestinal ◽  
Plasma Motilin ◽  
Opioid Receptor Agonists

In the first part of this study, we compared the effects of morphine and trimebutine, two opioid receptor agonists, on small intestinal motility and plasma motilin in dogs. Morphine (100 micrograms/kg iv for 10 min) induced first a typical vomiting myoelectric profile followed subsequently by a migrating electrical activity mimicking phase III of the migrating myoelectric complex; trimebutine (5 mg/kg iv for 10 min) initiated only a migrating phase III-like activity. Despite their different initial contractile effects, both agents induced a significant and similar rise in plasma motilin that preceded the beginning of the premature phase III. In the second portion of the study, naloxone, an opioid receptor antagonist, was infused to verify the influence of endogenous opiates on plasma motilin and on the migrating motor complex. Naloxone (2 mg/kg, then 0.5 mg.kg-1.h-1 iv) delayed significantly the cyclic recurrence of plasma motilin peak increases and of the phase IIIs. In some animals, where naloxone abolished the phase IIIs, the amplitude of the motilin peak increases was significantly diminished. These results suggest 1) that opioid administration increases plasma levels of motilin by a mechanism that is independent of the intestinal contractile activity, and 2) that endogenous opioids could be physiological inducers of plasma motilin increases in the conscious dog.

Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog

1984 ◽  
Vol 247 (6) ◽  
pp. G688-G694 ◽  
Author(s):  
Z. Itoh ◽  
M. Nakaya ◽  
T. Suzuki ◽  
H. Arai ◽  
K. Wakabayashi
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Intravenous Infusion ◽  
Contractile Activity ◽  
Contractile Force ◽  
Naturally Occurring ◽  
Gastrointestinal Motor ◽  
Plasma Motilin ◽  
Interdigestive Migrating Contractions ◽  
Gastrointestinal Contractile Activity

The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs. It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50–100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum. The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration. The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions. Like motilin, EM stimulated motor activity only during the interdigestive state. We conclude that EM induces IMC associated with the release of endogenous motilin in the dog.

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

2012 ◽  
Vol 302 (2) ◽  
pp. R233-R241 ◽  
Author(s):  
Atsushi Ogawa ◽  
Erito Mochiki ◽  
Mitsuhiro Yanai ◽  
Hiroki Morita ◽  
Yoshitaka Toyomasu ◽  
...  
Keyword(s):  
Conscious Dogs ◽  
Phase Iii ◽  
Motility Index ◽  
Growth Hormone Secretagogue ◽  
Plasma Motilin ◽  
Interdigestive Migrating Contractions ◽  
Rats And Mice ◽  
The Relationship ◽  
Gi Motility

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [d-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [d-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.

Periodic contractions of the canine gallbladder during the interdigestive state

1981 ◽  
Vol 240 (2) ◽  
pp. G183-G189 ◽  
Author(s):  
Z. Itoh ◽  
I. Takahashi
Keyword(s):  
Phase Ii ◽  
Intravenous Infusion ◽  
Motor Response ◽  
Contractile Activity ◽  
Direct Action ◽  
Initial Period ◽  
Contractile Force ◽  
Force Transducers ◽  
The Mean ◽  
Interdigestive Migrating Contractions

Interdigestive contractile activity of the gallbladder, the stomach, and the duodenum was measured by means of chronically implanted force transducers in five conscious dogs. During the interdigestive state, contractions of the gallbladder were identified to be closely associated with the initial period of phase II of the interdigestive migrating contractions (IMC) in the duodenum. The mean contractile force of the gallbladder during this phase was 6.5 +/- 0.77 g, which corresponded to approximately 80% of the force of the postprandial contractions. When the duodenum exhibited phase II contractions, the gallbladder had already returned to the resting level. Intravenous infusion of synthetic motilin induced IMC in the stomach and duodenum and during the initial period of motor response of the duodenum reproduced contractions in the gallbladder that were identical to the natural contractions as to their period and pattern. We cannot yet ascribe the interdigestive contractions observed in the gallbladder to the direct action of motilin, but the present study clearly indicates that the gallbladder contracts even in the interdigestive state, and the contractions are associated with the phase II contractions in the duodenum.

Effects of l-leucine, its 2-keto acid metabolite and its nonmetabolized analogue on rat tumoral islet cell function

1988 ◽  
Vol 1 (1) ◽  
pp. 69-76 ◽  
Author(s):  
V. Leclercq-Meyer ◽  
J. Marchand ◽  
A. Sener ◽  
F. Blachier ◽  
W. J. Malaisse
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Islet Cells ◽  
Adenine Nucleotides ◽  
Secretory Response ◽  
Acid Metabolite ◽  
Dual Effect ◽  
Islet Cell Function ◽  
Insulinoma Cells ◽  
Stimulation Of

ABSTRACT l-Leucine and 2-ketoisocaproate stimulated insulin release from perifused rat tumoral islet cells (RINm5F line). The secretory response coincided with an increase in the intracellular ATP/ADP ratio, a stimulation of 45Ca outflow from cells perifused in the presence of extracellular Ca2+, and an increase in 32P efflux from cells prelabelled with radioactive orthophosphate. In contrast to d-glucose, however, l-leucine or 2-ketoisocaproate failed to decrease 86Rb outflow, to inhibit 45Ca outflow from cells perifused in the absence of Ca2+ and to enhance the labelling of inositol-containing phospholipids in cells exposed to myo-[2-3H]inositol. These findings suggest that d-glucose, l-leucine and 2-ketoisocaproate exert dissimilar effects on the subcellular distribution of adenine nucleotides and/or 86Rb. The nonmetabolized analogue of l-leucine, 2-aminobicyclo-[2.2.1]heptane-2-carboxylic acid (BCH), also caused an initial stimulation of insulin release and 32P efflux, but this was soon followed by a severe and irreversible inhibition of insulin output, associated with a permanent enhancement of 86Rb outflow. The dual ionic and secretory response to BCH is interpreted in the light of its dual effect on the catabolism of endogenous amino and fatty acids, and raises the view that BCH could be used to interfere with the function of insulinoma cells.

Relationship of plasma motilin concentration to fat ingestion, duodenal acidification and alkalinization, and migrating motor complexes in dogs

1981 ◽  
Vol 59 (2) ◽  
pp. 180-187 ◽  
Author(s):  
J. E. T. Fox ◽  
N. S. Track ◽  
E. E. Daniel
Keyword(s):  
Species Difference ◽  
Maximal Activity ◽  
Significant Rise ◽  
Migrating Motor Complex ◽  
Phase Iii ◽  
Complex Activity ◽  
Duodenal Motility ◽  
Motor Complex ◽  
Duodenal Acidification ◽  
Plasma Motilin

Plasma motilin concentrations were measured in dogs following duodenal acidification and alkalinization and gastric instillation of fat. Antral and duodenal motility were recorded concurrently using intraluminal manometry. Alkalinization of the duodenum produced an increase in antral and duodenal motility and a significant rise in plasma motilin. Alkaline infusions at 5 mL/min into the duodenum initiated phase III of a migrating motor complex both in the antrum and in the duodenum. Duodenal acid infusions produced no change in plasma motilin concentrations while inhibiting antral motility and stimulating duodenal motility for the duration of the infusion. Gastric instillation of 60 g fat produced a 25% increase above basal motilin levels at 50 min after instillation. Motilin levels monitored during spontaneous migrating motor complexes showed peak motilin levels occurring during maximal activity of the antral duodenal region in seven out of nine motor complexes examined but motilin peaks also occurred without migrating complexes being present in this area and, as well, complexes occurred when motilin was undetectable. These results taken together with our other studies in man confirm that a true species difference exists between man and dog in the hormonal motor response to duodenal alkalinization. Although a relationship appears to exist between the appearance of maximal migrating motor complex activity in the gastroduodenal area and plasma motilin concentrations in dogs as in humans, the motilin peaks are probably neither necessary nor sufficient to induce phase III activity.

Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell

1996 ◽  
Vol 134 (5) ◽  
pp. 617-625 ◽  
Author(s):  
Per Lindström ◽  
Janove Sehlin ◽  
Barbara J Frankel
Keyword(s):  
B Cell ◽  
Insulin Release ◽  
Cell Biology ◽  
Glucose Utilization ◽  
Islet Cells ◽  
Insulin Response ◽  
Chinese Hamster ◽  
Cytoplasmic Calcium ◽  
Essentially Normal ◽  
Channel Agonist

Lindström P. Sehlin J, Frankel BJ. Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell. Eur J Endocrinol 1996:134:617–25. ISSN 0804–4643 To characterize insulin release and cytoplasmic free Ca2+ [Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-3H]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2, The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4−, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+]i in 85% of the normal (presumably B) cells. In diabetic cells, the [Ca2+]i response was delayed, subnormal and only observed in 23% of the cells. When perchlorate or another Ca2+ channel agonist, 10 μmol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61–67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K+-induced insulin release was decreased in diabetic islets. The K+ -induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2−]i and exocytosis appear defective in the diabetic Chinese hamster B cell. Per Lindström, Department of Histology and Cell Biology, Umea University, S-901 87 Umea, Sweden

Extracellular calcium and adrenergic and cholinergic effects on islet beta-cell function

1976 ◽  
Vol 231 (4) ◽  
pp. 1246-1249 ◽  
Author(s):  
IM Burr ◽  
AE Slonim ◽  
V Burke ◽  
T Fletcher
Keyword(s):  
Insulin Release ◽  
Calcium Concentration ◽  
Direct Evidence ◽  
Cell Function ◽  
Insulin Response ◽  
Calcium Content ◽  
Biphasic Insulin Release ◽  
Perifusion System ◽  
Cholinergic Effects

An in vitro perifusion system utilizing collagen-medium calcium on the dynamics of insulin release as induced by acetylcholine (ACh) stimulation (in the presence of glucose, 2.4 mM) and as modified by prior perfusion of islets in epinephrine. Continuous challenge with ACh produces a biphasic insulin release response, both phases of which are reduced when the medium calcium concentration is reduced during stimulation; when the calcium content is reduced during an initial perifusion period of 30 min and then replaced during subsequent stimulation only the first phase of the response to ACh is affected; perifusion with epinephrine prior to stimulation with ACh produces enhancement of both phases of ACh-induced insulin release when calcium in both media is normal. However,.when this experiment is repeated utilizing a medium with low calcium content during the period of exposure to epinephrine the priming effect of epinephrine on the subsequent insulin response to ACh is abolished (in fact, reversed). These studies provide direct evidence for a role for calcium in mediating an effect of epinephrine on insulin release. Further, the data suggest that epinephrine affects Ca transport in islets in some manner beyond stimulating net efflux from islets, perhaps by enhancing membrane binding of calcium.

Sensitivity to Cd2+ but resistance to Ni2+ of Ca2+ inflow into rat pancreatic islets

1990 ◽  
Vol 258 (3) ◽  
pp. E529-E533 ◽  
Author(s):  
P. O. Plasman ◽  
M. Hermann ◽  
A. Herchuelz ◽  
P. Lebrun
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Islet Cells ◽  
Excitable Cells ◽  
45Ca Uptake ◽  
Rat Pancreatic Islets ◽  
Cell Plasma ◽  
Different Types ◽  
45Ca Efflux ◽  
Ca2 Channels

The presence of different types [long lasting (L) and transient (T)] of active voltage-operated Ca2+ channels in islet cells was investigated by comparing the effects of Cd2+, Ni2+, and 1,4-dihydropyridines on 45Ca uptake, 45Ca efflux, and insulin release in intact rat pancreatic islets. In several other excitable cells the L-channel has been shown to be modulated by 1,4-dihydropyridines and Cd2+, whereas the T-channel was reported to be sensitive to Ni2+. Nifedipine and Cd2+ inhibited whereas BAY K 8644 enhanced the glucose (11.1, 22.2 mM)-stimulated short-term 45Ca uptake, 45Ca efflux, and insulin release. In contrast, the stimulatory effects of glucose (11.1, 22.2 mM) on 45Ca uptake, 45Ca efflux, and insulin release were unaffected by Ni2+. These findings confirm that glucose provokes Ca2+ entry mainly by activating voltage-sensitive Ca2+ channels of the L-type and suggest that the B-cell plasma membrane is not equipped with active T-type Ca2+ channels.

scholarly journals Cytotoxic effects of streptozotocin and N-nitrosomethylurea on the pancreatic B cells with special regard to the role of nicotinamide–adenine dinucleotide

1974 ◽  
Vol 140 (3) ◽  
pp. 487-494 ◽  
Author(s):  
Rolf Gunnarsson ◽  
Christian Berne ◽  
Claes Hellerström
Keyword(s):  
Insulin Release ◽  
Islet Cells ◽  
Cytotoxic Action ◽  
Glucose Residue ◽  
Cytotoxic Effects ◽  
Pancreatic B Cells ◽  
Effect Of Glucose ◽  
Oxidation Of Glucose ◽  
Nad Depletion

The effects on the pancreatic B cell of streptozotocin and its aglucone derivative N-nitrosomethylurea were investigated in obese–hyperglycaemic mice and their lean littermates. Both streptozotocin and N-nitrosomethylurea were found to be B-cytotoxic although N-nitrosomethylurea produced less islet damage. Both substances decreased the concentrations of NAD+ in the islet cells to about 10% of the control values within 2h after injection. This NAD+ depletion was prevented by injection of nicotinamide 10min after the administration of streptozotocin or N-nitrosomethylurea. In islets taken from animals 10min after injection of streptozotocin or N-nitrosomethylurea there was no stimulatory effect of glucose on the respiration or insulin release and the oxidation of glucose was markedly decreased. Addition of nicotinamide (10mm) to the incubated islets restored glucose stimulation of both the oxygen consumption and insulin release. It is concluded that islet NAD+ depletion is probably important for the B-cytotoxin action of N-nitrosomethylurea and streptozotocin. The glucose residue in the streptozotocin molecule may potentiate the B-cytotoxic action of this drug in mice.

Sign in / Sign up

Export Citation Format

Share Document