scholarly journals Mechanisms of the stimulation of insulin release by oxytocin in normal mouse islets

1991 ◽  
Vol 276 (1) ◽  
pp. 169-174 ◽  
Author(s):  
Z Y Gao ◽  
G Drews ◽  
J C Henquin
Keyword(s):  
B Cells ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Islet Cells ◽  
Inositol Phosphate ◽  
Resting Potential ◽  
Phosphoinositide Metabolism ◽  
Mouse Islets ◽  
45Ca Efflux ◽  
Stimulation Of

Oxytocin (OT) produced a dose-dependent increase in somatostatin, glucagon and insulin release by isolated mouse islets. A small effect on somatostatin release was observed with 0.1 nM-OT, but 1-10 nM-OT was required to affect A- and B- cells significantly. The effects of OT on somatostatin and glucagon release were similar in the presence of 3 mM- and 10 mM-glucose. No change in insulin release was produced by OT in 3 mM-glucose, but a stimulation was still observed in the presence of a maximally effective concentration of glucose (30 mM). The increase in insulin release produced by OT (in 15 mM-glucose) was accompanied by small accelerations of 86Rb and 45Ca efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of OT on 86Rb efflux, attenuated that on 45Ca efflux, and abolished that on release. OT never inhibited 86Rb efflux. It did not affect the resting potential of B-cells, but slightly increased the Ca2(+)-dependent electrical activity induced by 15 mM-glucose. OT did not affect cyclic AMP levels, but increased inositol phosphate levels in islet cells. It is suggested that the amplification of glucose-induced insulin release that OT produces is due to a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than to a change in cyclic AMP levels or a direct action on the membrane potential. Since OT is present in the pancreas, it is possible that it exerts a neuropeptidergic control of the islet function.

scholarly journals A role for calcium in the breakdown of inositol phospholipids in intact and digitonin-permeabilized pancreatic islets

1986 ◽  
Vol 238 (3) ◽  
pp. 773-779 ◽  
Author(s):  
L Best
Keyword(s):  
Lipid Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Islet Cells ◽  
Inositol Phosphate ◽  
Significant Stimulation ◽  
Inositol Phospholipids ◽  
Inositol Phosphate Production ◽  
Small Inhibition ◽  
Stimulation Of

Glucose (20 mM) and 4-methyl-2-oxopentanoate (10 mM) both caused a pronounced stimulation of insulin release and of [3H]inositol phosphate production in rat pancreatic islets prelabelled with myo-[3H]inositol. Secretory responses to these nutrients were markedly impaired by lowering the Ca2+ concentration of the incubation medium to 10(-4)M or less, whereas stimulated inositol phosphate production was sensitive to Ca2+ within the range 10(-6)-10(-4)M. Inositol phosphate formation in response to carbamoylcholine was also found to be dependent on the presence of 10(-5)M-Ca2+ or above. Raising the concentration of K+ in the medium resulted in a progressive, Ca2+-dependent stimulation of inositol phosphate production in islets, although no significant stimulation of insulin release was observed. In islets prelabelled with myo[3H]inositol, then permeabilized by exposure to digitonin, [3H]inositol phosphate production could be triggered by raising the Ca2+ concentration from 10(-7) to 10(-5)M. This effect was dependent on the concentration of ATP and the presence of Li+, and involved detectable increases in the levels of InsP3 and InsP2 as well as InsP. A potentiation of inositol phosphate production by carbamoylcholine was observed in permeabilized islets at lower Ca2+ concentrations, although nutrient stimuli were ineffective. No significant effects were observed with guanine nucleotides or with neomycin, although NADH produced a modest increase and adriamycin a small inhibition of inositol phosphate production in permeabilized islets. These results strongly suggest that Ca2+ ions play an important role in the stimulation of inositol lipid metabolism in islets in response to nutrient secretagogues, and that inositide breakdown may actually be triggered by Ca2+ entry into the islet cells.

Impairment by aminooxyacetate of ionic response to nutrients in pancreatic islets

1983 ◽  
Vol 245 (1) ◽  
pp. E38-E46
Author(s):  
P. Lebrun ◽  
W. J. Malaisse ◽  
A. Herchuelz
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Redox State ◽  
Islet Cells ◽  
Inhibitory Effect ◽  
High Concentration ◽  
Perifused Islets ◽  
45Ca Efflux ◽  
Reduced State ◽  
Stimulation Of

Aminooxyacetate, an inhibitor of transamination reactions, was recently reported to prevent the induction of a more reduced state in the cytosolic redox couple, as normally evoked by glucose or 2-ketoisocaproate in rat pancreatic islets. The cationic effects of aminooxyacetate were examined, therefore, in perifused islets prelabeled with either 86Rb or 45Ca. Aminooxyacetate augmented the outflow of 86Rb from the islets whether in the absence or presence of an exogenous nutrient and slightly impaired the capacity of nutrients, especially 2-ketoisocaproate, to decrease 86Rb outflow. Aminooxyacetate abolished the nutrient-induced rise in 45Ca efflux that normally results from the stimulation by glucose or 2-ketoisocaproate of 40Ca influx into the islet cells. Aminooxyacetate, however, failed to suppress the early inhibitory effect of nutrients on 45Ca efflux. The alteration by aminooxyacetate of the cationic response to nutrient secretagogues coincided with a suppression of insulin release, whereas the cationic response to a nonnutrient stimulation by a high concentration of extracellular K+ was unaffected by aminooxyacetate. These findings suggest that the induction of a more reduced cytosolic redox state represents an essential link between metabolic events and both the decrease in K+ conductance and stimulation of Ca2+ inflow in the process of nutrient-induced insulin release.

scholarly journals Vanadate stimulation of insulin release in normal mouse islets.

1991 ◽  
Vol 266 (32) ◽  
pp. 21649-21656
Author(s):  
A.Q. Zhang ◽  
Z.Y. Gao ◽  
P. Gilon ◽  
M. Nenquin ◽  
G. Drews ◽  
...  
Keyword(s):  
Insulin Release ◽  
Normal Mouse ◽  
Mouse Islets ◽  
Stimulation Of

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.

Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets.

1978 ◽  
Vol 235 (5) ◽  
pp. E493 ◽  
Author(s):  
E Gagerman ◽  
L A Idahl ◽  
H P Meissner ◽  
I B T�ljedal
Keyword(s):  
Membrane Potential ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Cyclic Gmp ◽  
Spike Activity ◽  
Obvious Effect ◽  
Ionic Fluxes ◽  
Mouse Islets ◽  
Silent State ◽  
Esterase Inhibitor

Acetylcholine potentiated the glucose-induced insulin release from microdissected mouse islets of Langerhans but had no effect on basal insulin release. Significant potentiation was obtained with 0.1 micron acetylcholine in the presence of 10 micron eserine and with 1 micron or more acetylcholine in the absence of a choline esterase inhibitor. Carbamylcholine, too, potentiated insulin release. Potentiation was blocked by methylatropine, whereas methylatropine alone had no effect on insulin release. Acetylcholine or carbamylcholine (5-500 micron) had no obvious effect on cyclic GMP or cyclic AMP in the islets. In the presence of 11.1 mM D-glucose, the membrane potential of beta-cells oscillated slowly between a polarized silent state of -50 to -55 mV and a depolarized active state of -33 to -39 mV, at which a fast spike activity occurred. Acetylcholine made the potential stay at the plateau and induced a continuous spike activity pattern. Atropine inhibited the electrical effects of acetylcholine but not those of glucose alone. It is suggested that cholinergic potentiation of insulin release is mediated by changes of transmembrane ionic fluxes, probably without the intervention of cyclic GMP or cyclic AMP.

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 Cyclic AMP agonists induce the phosphorylation of phospholipase C-τ and of a 76 kDa protein co-precipitated by anti-(phospholipase C-τ) monoclonal antibodies in BALB/c-3T3 cells. Relationship to inositol phosphate formation

1990 ◽  
Vol 272 (2) ◽  
pp. 297-303 ◽  
Author(s):  
N E Olashaw ◽  
S G Rhee ◽  
W J Pledger
Keyword(s):  
Monoclonal Antibodies ◽  
Growth Factor ◽  
Cyclic Amp ◽  
Phospholipase C ◽  
Cholera Toxin ◽  
Inositol Phosphate ◽  
Serine Phosphorylation ◽  
Intrinsic Activity ◽  
Phosphoinositide Metabolism ◽  
3T3 Cells

Previous studies have demonstrated enhanced phosphorylation of phospholipase C-tau (PLC-tau), a key regulatory enzyme in phosphoinositide metabolism, in cells treated with platelet-derived growth factor (PDGF) and epidermal growth factor, both of which act via specific receptor tyrosine kinases. Our studies on BALB/c-3T3 cells show that agents that promote cellular cyclic AMP accumulation also increase the phosphorylation, specifically the serine phosphorylation, of this enzyme. Increased phosphorylation of PLC-t (2-3-fold) was evident within 5-10 min of addition of isobutylmethylxanthine (IBMX) and either cholera toxin or forskolin to cells, and persisted for at least 3 h. Treatment of cells with cyclic AMP agonists also enhanced, with similar kinetics, the phosphorylation of a 76 kDa protein co-precipitated by anti-PLC-tau monoclonal antibodies. Brief exposure of cells to cholera toxin/IBMX or forskolin/IBMX decreased inositol phosphate formation induced by the GTP-binding protein (G-protein) activator aluminium fluoride by approx. 50%, but was without effect on PDGF-stimulated inositol phosphate formation. These findings suggest that PLC-tau, and perhaps the 76 kDa co-precipitated protein, are substrates of cyclic AMP-dependent protein kinase in BALB/c-3T3 cells: however, the lack of effect of cyclic AMP elevation on PDGF-stimulated inositol phosphate formation indicates that the intrinsic activity of PLC-tau is unaltered by cyclic AMP-mediated phosphorylation.

scholarly journals Effects of trifluoperazine and pimozide on stimulus–secretion coupling in pancreatic B-cells Suggestion for a role of calmodulin?

1981 ◽  
Vol 196 (3) ◽  
pp. 771-780 ◽  
Author(s):  
Jean-Claude Henquin
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Islet Cells ◽  
Antipsychotic Agents ◽  
Secretory Process ◽  
Dependent Inhibition ◽  
Net Uptake ◽  
Stimulus Secretion Coupling ◽  
Two Phases

The possible involvement of calmodulin in insulin release was evaluated by studying the effects on intact islets of trifluoperazine and pimozide, two antipsychotic agents known to bind strongly to calmodulin in cell-free systems. Trifluoperazine (10–100μm) produced a dose- and time-dependent inhibition of the two phases of glucose-stimulated insulin release. The effect was not reversible by simple washing of the drug, but could be prevented by cytochalasin B or theophylline. Trifluoperazine also inhibited the release induced by glyceraldehyde, oxoisocaproate, tolbutamide or barium, but not that stimulated by 10mm-theophylline or 1mm-3-isobutyl-1-methylxanthine. Pimozide (0.5–10μm) also produced a dose-dependent inhibition of insulin release triggered by glucose, leucine or barium, but did not affect the release induced by methylxanthines. Glucose utilization by islet cells was not modified by trifluoperazine (25μm), which slightly increased cyclic AMP concentration in islets incubated without glucose. The drug did not prevent the increase in cyclic AMP concentration observed after 10min of glucose stimulation, but suppressed it after 60min. Basal or glucose-stimulated Ca2+ influx (5min) was unaffected by 25μm-trifluoperazine, whereas Ca2+net uptake (60min) was inhibited by 20%. Glucose-stimulated Ca2+ uptake was almost unaffected by pimozide. In a Ca2+-free medium, trifluoperazine decreased Ca2+ efflux from the islets and did not prevent the further decrease by glucose; in the presence of Ca2+, the drug again decreased Ca2+ efflux and inhibited the stimulation normally produced by glucose. In the absence of glucose, trifluoperazine lowered the rate of Rb+ efflux from the islets, decreased Rb+ influx (10min), but did not affect Rb+ net uptake (60min). It did not interfere with the ability of glucose to decrease Rb+ efflux rate further and to increase Rb+ net uptake. The results show thus that trifluoperazine does not alter the initial key events of the stimulus–secretion coupling. Its inhibition of insulin release suggests a role of calmodulin at late stages of the secretory process.

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