Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro

1990 ◽  
Vol 127 (2) ◽  
pp. 335-340 ◽  
Author(s):  
L. C. Wilkes ◽  
C. J. Bailey ◽  
M. G. Thompson ◽  
J. M. Conlon ◽  
K. D. Buchanan
Keyword(s):  
Insulin Release ◽  
Pancreatic Polypeptide ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Second Phase ◽  
Rinm5f Cells ◽  
Maximum Increase ◽  
Gastrin Releasing Peptide ◽  
Mouse Islets

ABSTRACT Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5·6 mmol glucose/1, 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16·7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2·8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11·1 mmol/l. At 5·6 mmol glucose/l, GRP (100 pmol/1–100 nmol/l) increased (by 50–70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 μmol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores. Journal of Endocrinology (1990) 127, 335–340

DEVELOPMENT OF PATHWAYS OF INSULIN SECRETION IN THE RABBIT

1975 ◽  
Vol 64 (2) ◽  
pp. 349-361 ◽  
Author(s):  
R. D. G. MILNER ◽  
F. N. LEACH ◽  
M. A. ASHWORTH ◽  
A. CSER ◽  
P. M. B. JACK
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Similar Rate ◽  
Extracellular Glucose ◽  
Cell Changes ◽  
Foetal Pancreas ◽  
Stimulation Of

SUMMARY Insulin release was studied in vitro using pieces of pancreas from rabbits of between 24 days gestational age and 6 weeks postnatal age. When allowance was made for the fraction of pancreas which was endocrine, 16·5 mm-glucose caused increasing stimulation of insulin release as development advanced and 3·3 mm-glucose caused a similar rate of secretion at all ages. Secretion was not significantly influenced by insulin destruction in the incubation medium. Glucagon (5 μg/ml) did not stimulate insulin secretion from 24-day foetal pancreas but did so postnatally. Theophylline (1 mmol/l) stimulated insulin release at all ages and was equipotent on 24-day foetal pancreas in 3·3 or 16·5 mm-glucose. The stimulation of insulin release from 24-day foetal pancreas by 1 mm-theophylline occurred in the absence of extracellular glucose, pyruvate, fumarate and glutamate and in the presence of mannoheptulose and 2-deoxyglucose (each 3 mg/ml). Adrenaline (1 μmol/l) and diazoxide (250 μg/ml) abolished or attenuated the stimulation of insulin release by glucose, leucine plus arginine or theophylline from 24-day foetal, 1 day and 6 weeks postnatal pancreas. The stimulation of insulin release from 6-week-old pancreas by 1 mm-barium was blocked by adrenaline and diazoxide but the effect became less with increasing immaturity. The experimental results illustrate some of the ways in which insulin secretion by the rabbit β cell changes as a function of development and draw attention to the importance of glucose and cyclic adenosine monophosphate in this process.

HUMAN FOETAL PANCREATIC INSULIN SECRETION IN RESPONSE TO IONIC AND OTHER STIMULI

1971 ◽  
Vol 51 (2) ◽  
pp. 323-332 ◽  
Author(s):  
R. D. G. MILNER ◽  
A. J. BARSON ◽  
M. A. ASHWORTH
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Β Cells ◽  
Pancreatic Insulin ◽  
Foetal Life ◽  
Acinar Tissue ◽  
Foetal Pancreas

SUMMARY Pieces of human foetal pancreas were incubated under control conditions and in media containing different stimuli of insulin release. Insulin secretion was stimulated from the pancreases of foetuses (83–625 g body weight) which were of 16–24 weeks gestational age. Potassium (60 mmol/l), barium (2·54 mmol/l) and ouabain (10−5 mol/l) were effective stimuli in all experiments. Glucagon (5 μg/ml), theophylline (1 mmol/l) and dibutyryl 3′,5′-cyclic adenosine monophosphate (1 mmol/l) stimulated insulin secretion in media containing 0, 0·6 or 3·0 mg glucose/ml. Theophylline and dibutyryl 3′,5′-cyclic adenosine monophosphate were effective in all experients and glucagon stimulated insulin release in four out of six experiments. At all ages studied, histological examination of the pancreas after each experiment revealed islets of Langerhans containing β cells. In most cases the islets were of the mantle type but occasionally bipolar islets were seen. Cellular normality, as judged by light microscopy, was preserved after periods of incubation for up to 5½ h. Glycogen was demonstrable in the pancreatic acinar tissue but not in the islets. The results of these experiments indicate that, between the 16th and 24th week of foetal life, the human β cell is capable of releasing insulin in vitro when stimulated appropriately.

Dobutamine Antagonizes Epinephrine's Biochemical and Cardiotonic Effects 

1998 ◽  
Vol 89 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Richard C. Prielipp ◽  
Drew A. MacGregor ◽  
Roger L. Royster ◽  
Neal D. Kon ◽  
Michael H. Hines ◽  
...  
Keyword(s):  
Artery Bypass ◽  
Phase 1 ◽  
Human Lymphocytes ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Production ◽  
Isobolographic Analysis ◽  
Camp Generation ◽  
Vitro Model

Background Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects. Methods The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination. Results In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. Conclusions Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.

The antilipolytic agent 3,5-dimethylpyrazole inhibits insulin release in response to both nutrient secretagogues and cyclic adenosine monophosphate agonists in isolated rat islets

Metabolism ◽  
2002 ◽  
Vol 51 (1) ◽  
pp. 110-114 ◽  
Author(s):  
P. Masiello ◽  
M. Novelli ◽  
M. Bombara ◽  
V. Fierabracci ◽  
S. Vittorini ◽  
...  
Keyword(s):  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Rat Islets ◽  
Isolated Rat Islets ◽  
Isolated Rat

scholarly journals The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity

2011 ◽  
Vol 193 (6) ◽  
pp. 1009-1020 ◽  
Author(s):  
Martijn Gloerich ◽  
Marjolein J. Vliem ◽  
Esther Prummel ◽  
Lars A.T. Meijer ◽  
Marije G.A. Rensen ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Negative Regulator ◽  
Camp Signaling ◽  
Nuclear Pore ◽  
Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Wide Range

Cyclic adenosine monophosphate (cAMP) is a second messenger that relays a wide range of hormone responses. In this paper, we demonstrate that the nuclear pore component RanBP2 acts as a negative regulator of cAMP signaling through Epac1, a cAMP-regulated guanine nucleotide exchange factor for Rap. We show that Epac1 directly interacts with the zinc fingers (ZNFs) of RanBP2, tethering Epac1 to the nuclear pore complex (NPC). RanBP2 inhibits the catalytic activity of Epac1 in vitro by binding to its catalytic CDC25 homology domain. Accordingly, cellular depletion of RanBP2 releases Epac1 from the NPC and enhances cAMP-induced Rap activation and cell adhesion. Epac1 also is released upon phosphorylation of the ZNFs of RanBP2, demonstrating that the interaction can be regulated by posttranslational modification. These results reveal a novel mechanism of Epac1 regulation and elucidate an unexpected link between the NPC and cAMP signaling.

scholarly journals Thrombin-induced gap formation in confluent endothelial cell monolayers in vitro

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 549-556 ◽  
Author(s):  
M Laposata ◽  
DK Dovnarsky ◽  
HS Shin
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Gap Formation ◽  
Culture Dish ◽  
Cell Monolayers ◽  
Umbilical Vein Endothelial Cells

Abstract When thrombin is incubated with confluent monolayers of human umbilical vein endothelial cells in vitro, there is a change in the shape of the endothelial cells that results in gaps in the monolayer, disrupting the integrity of the endothelium and exposing the subendothelium. Using a grid assay to measure this phenomenon, we observed that up to 80% of the surface area once covered by cells was uncovered after a 15-min incubation with 10(-2) U/ml (10(-10)M) thrombin. The effect was apparent within 2 min and did not remove cells from the surface of the culture dish. The gaps in the monolayer completely disappeared within 2 hr after exposure to thrombin. The effect of thrombin was inhibited by preincubation of thrombin with hirudin or antithrombin III plus heparin or by preincubation of the monolayers with dibutyryl cyclic adenosine monophosphate (dbcAMP). Histamine also induced gap formation in endothelial cell monolayers. Both pyrilamine and cimetidine prevented the histamine-induced effect, but they had no effect on thrombin- induced gap formation. Intact monolayers were not disrupted by bradykinin, serotonin, C5a, or C3a. Our results suggest that small amounts of thrombin can induce repeated and transient exposure of the subendothelium, a situation believed to be conducive to atherogenesis and thrombosis.

Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets

1986 ◽  
Vol 250 (2) ◽  
pp. E107-E113 ◽  
Author(s):  
H. Kofod ◽  
B. Hansen ◽  
A. Lernmark ◽  
C. J. Hedeskov
Keyword(s):  
Glutamate Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Insulin Release ◽  
Maximal Effect ◽  
Terminal Sequence ◽  
Terminal Part ◽  
Mouse Pancreatic Islets ◽  
Glutamate Dehydrogenase Activity ◽  
Mouse Islets

Peptides representing the C-terminal end of secretin were synthetized and their effects tested along with secretin on column-perifused isolated mouse pancreatic islets. Insulin release induced by 10 mmol/l D-glucose was potentiated by secretin tested in a concentration range of 0.01-10 micrograms/ml; the maximal effect was obtained with 1 microgram/ml secretin. This effect was mimicked by 50-500 micrograms/ml NH2-Leu-Leu-Gln-Gly-Leu-Val-NH2, [S-(22-27)], which represents an amidated C-terminal sequence of the secretin molecule. The consecutive smaller secretin C-terminal peptides had either no effects [Val-NH2, S-(24-27)] or only marginally [S-(26-27), S-(23-27)] potentiating effects on insulin release in the presence of 10 mmol/l D-glucose. The effects of secretin and S-(22-27) were not influenced by 2 mmol/l glutamine. The intact hormone and the five synthetic peptides as well as Val-NH2 had no stimulatory effect on islet glutamate dehydrogenase activity. In fact, S-(23-27), S-(24-27), and S-(25-27) inhibited the islet glutamate dehydrogenase activity, the activation by which amino acids and amino acid derivatives are known to elicit a potentiation of insulin release. Our results suggest that the C-terminal part is important to the marked potentiation of glucose-induced insulin release in vitro by secretin.

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