scholarly journals Mechanism of 3-phenylpyruvate-induced insulin release. Secretory, ionic and oxidative aspects

1983 ◽  
Vol 210 (3) ◽  
pp. 913-919 ◽  
Author(s):  
A Sener ◽  
M Welsh ◽  
P Lebrun ◽  
P Garcia-Morales ◽  
M Saceda ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Inhibitory Effect ◽  
Secretory Response ◽  
Acid Transport ◽  
O2 Uptake ◽  
Net Uptake ◽  
High Concentrations ◽  
Stimulation Of

1. 3-Phenylpyruvate caused a dose-related stimulation of insulin release from rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of 5.6 or 8.3 mM-D-glucose. 2. 3-Phenylpyruvate inhibited insulin release evoked by high concentrations of D-glucose (16.7 or 27.8 mM) or 4-methyl-2-oxopentanoate (10.0 mM). This inhibitory effect appeared to be attributable to impairment of 2-oxo-acid transport into the mitochondria, with resulting inhibition of D-glucose, pyruvate or 4-methyl-2-oxopentanoate oxidation. 3. 3-Phenylpyruvate failed to affect the oxidation of, and secretory response to, L-leucine, and did not augment insulin release evoked by a non-metabolized analogue of the latter amino acid. 4. L-Glutamine augmented 3-phenylpyruvate-induced insulin release. The release of insulin evoked by the combination of 3-phenylpyruvate and L-glutamine represented a sustained phenomenon, abolished in the absence of extracellular Ca2+ or the presence of menadione and potentiated by theophylline. 5. Whether in the presence or in the absence of L-glutamine, the secretory response to 3-phenylpyruvate coincided with an increase in O2 uptake, a decrease in K+ conductance, a stimulation of both Ca2+ inflow and 45Ca2+ net uptake and an increase in cyclic AMP content. 6. It is concluded that the release of insulin induced by 3-phenylpyruvate displays features classically encountered when the B-cell is stimulated by nutrient secretagogues, and is indeed attributable to an increase in nutrient catabolism.

scholarly journals Effects of growth factors on hormonal stimulation of amino acid transport in primary cultures of rat hepatocytes

1983 ◽  
Vol 210 (2) ◽  
pp. 361-366 ◽  
Author(s):  
P Auberger ◽  
M Samson ◽  
A Le Cam
Keyword(s):  
Growth Factors ◽  
Amino Acid ◽  
Growth Factor ◽  
Cyclic Amp ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Acid Transport ◽  
Hormonal Stimulation ◽  
Hormonal Effect ◽  
Stimulation Of

In primary cultures of rat hepatocytes, epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and foetal-calf serum (FCS) prevented the stimulation of amino acid transport by glucagon (cyclic AMP-dependent) and by catecholamines (cyclic AMP-independent), but not by insulin. The insulin effect, as well as the effect of other hormones, were totally inhibited by thrombin through a mechanism independent of its proteolytic activity. The inhibitory effect of growth factors, not found in freshly isolated hepatocytes, was expressed very early in culture (4h). Induction of tyrosine aminotransferase by glucagon or dexamethasone, which, like stimulation of transport, represents a late hormonal effect, was not affected by EGF, PDGF or FCS, but was inhibited by thrombin. In contrast, none of the rapid changes in protein phosphorylation caused by hormones was altered by growth factors. Thus the inhibition by growth factors of hormonal stimulation of transport presumably involves late step(s) in the cascade of events implicated in this hormonal effect.

Respiratory, ionic, and functional effects of succinate esters in pancreatic islets

1993 ◽  
Vol 264 (3) ◽  
pp. E428-E433 ◽  
Author(s):  
W. J. Malaisse ◽  
J. Rasschaert ◽  
M. L. Villanueva-Penacarrillo ◽  
I. Valverde
Keyword(s):  
Succinic Acid ◽  
Insulin Release ◽  
Methyl Esters ◽  
O2 Uptake ◽  
Biosynthetic Activity ◽  
Insulin Secretagogues ◽  
Net Uptake ◽  
Characteristic Features ◽  
45Ca Efflux ◽  
Stimulation Of

The methyl esters of succinic acid were introduced a few years ago as new potent insulin secretagogues. In the present study, they were found to increase O2 uptake by rat islets incubated in the absence or presence of D-glucose; to decrease 86Rb outflow from prelabeled islets; to stimulate biosynthetic activity in the islets, with a preferential effect on the synthesis of proinsulin; to inhibit 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca2+ but to augment 45Ca net uptake and to cause a biphasic stimulation of 45Ca outflow in islets incubated or perifused in the presence of extracellular Ca2+; and to evoke a biphasic stimulation of insulin release. The insulinotropic action of these methyl esters coincided with a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration, was concentration related in the 2-10 mM range, failed to be duplicated by succinic acid, displayed both Ca2+ dependency and resistance to a lowering of extracellular pH, and was operative in the absence of D-glucose whether or not the islets were stimulated by non-nutrient secretagogues. It is concluded that the respiratory, cationic, biosynthetic, and secretory responses of the islets to succinate methyl esters display the characteristic features usually encountered in the process of nutrient-stimulated insulin release.

scholarly journals Short-term stimulation of Na+-dependent amino acid transport by dibutyryl cyclic AMP in hepatocytes. Characteristics and partial mechanism

1987 ◽  
Vol 241 (3) ◽  
pp. 737-743 ◽  
Author(s):  
S K Moule ◽  
N M Bradford ◽  
J D McGivan
Keyword(s):  
Amino Acid ◽  
Cyclic Amp ◽  
Amino Acid Transport ◽  
Acid Transport ◽  
Short Term ◽  
Membrane Hyperpolarization ◽  
Alanine Transport ◽  
Cell Plasma ◽  
Time Courses ◽  
Stimulation Of

The short-term protein-synthesis-independent stimulation of alanine transport in hepatocytes was further investigated. Cyclic AMP increased the Vmax. of alanine transport. Amino acid transport via systems A, ASC and N was stimulated. A good correlation was found between the initial rate of transport and the cell membrane potential as calculated from the distribution of Cl-. Cyclic AMP increased the rate of alanine transport, stimulated Na+/K+ ATPase (Na+/K+-transporting ATPase) activity and caused membrane hyperpolarization. The time courses and cyclic AMP dose-dependencies of all three effects were similar. Ouabain abolished the effect of cyclic AMP on Cl- distribution and on transport of alanine. The effect of cyclic AMP on alanine transport and Cl- distribution was mimicked by the antibiotic nigericin; the effect of nigericin was also abolished by ouabain. It is concluded that the effect of cyclic AMP on transport is mediated via membrane hyperpolarization. It is suggested that the primary action of cyclic AMP is to increase the activity of an electroneutral Na+/K+-exchange system in the liver cell plasma membrane, thus hyperpolarizing the membrane by stimulating the electrogenic Na+/K+ ATPase.

Effect of calcium on uptake of α-aminoisobutyric acid by parathyroid glands

1963 ◽  
Vol 205 (5) ◽  
pp. 816-820 ◽  
Author(s):  
Lawrence G. Raisz ◽  
James E. O'Brien
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Calcium Concentration ◽  
Inhibitory Effect ◽  
Magnesium Concentration ◽  
Acid Transport ◽  
Bicarbonate Buffer ◽  
Hormone Synthesis ◽  
Aminoisobutyric Acid ◽  
High Concentrations

The uptake of α-aminoisobutyric acid (AIB) has been used as a model for the study of amino acid transport in the parathyroid gland. Freshly excised, whole rat parathyroids rapidly took up AIB when incubated in Krebs bicarbonate buffer under 5% CO2, 95% O2 at 37 C, with glucose as the only nutrient. Uptake was inversely proportional to calcium concentration in the medium over the range of 0.75 to 2.25 mm/ liter. Increasing magnesium concentration enhanced AIB uptake. Although AIB uptake was decreased in the absence of phosphate there was no stimulatory effect of increasing phosphate concentration from 0.5 to 3.0 mm/liter. Strontium had an inhibitory effect on uptake but was not as effective as calcium on an equimolar basis. High concentrations of leucine and glycine caused inhibition of uptake as did acidifying the medium to pH 7.1. Growth hormone, vitamin D, parathyroid extract, and hydrocortisone were without effect. AIB uptake of thyroid, kidney, muscle, and liver were not inhibited by calcium. The hypothesis that changes in calcium concentration control parathyroid hormone synthesis by inhibition of amino acid transport at the cell membrane is presented.

Modulation of Amino Acid Transport in Rat Liver Slices by Tissue Preincubation

1980 ◽  
Vol 35 (11-12) ◽  
pp. 1019-1023 ◽  
Author(s):  
Volker Ehrhardt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Liver ◽  
Amino Acid Transport ◽  
Specific Substrate ◽  
Acid Transport ◽  
Liver Slices ◽  
High Concentrations ◽  
Preincubation Medium ◽  
Stimulation Of

In rat liver slices, a prolonged preincubation resulted in a stimulation of AIB and alanine uptake. The increase of transport of both amino acids can be ascribed to a reduction of Kt without an alteration of Vt. The enhancement of transport seems to be restricted to the A mediation as indicated by the findings that only the Na+-dependent, MeAIB-inhibitable portion of AIB transport was increased by the prolonged preincubation, and, furthermore, that the uptake of cysteine, a specific substrate for system ASC in liver cells, was not affected. The effect of an extended preincubation on AIB transport was abolished by the addition of high concentrations of AIB and alanine to the preincubation medium. Several other amino acids tested did not affect the increase of AIB transport. The observed stimulation of transport seems not to be due to the derepression of the synthesis of transport proteins, as cycloheximide and 5-azacytidine did not block the increase of AIB uptake. The enhancement of amino acid transport does not appear to be a result of a release from transinhibition since the uptake of alanine was markedly enhanced after 3 h of preincubation while the alanine concentrations in the incubated liver slices did not change significantly.

scholarly journals High concentrations of exogenous arachidonate inhibit calcium mobilization in platelets by stimulation of adenylate cyclase

1988 ◽  
Vol 253 (1) ◽  
pp. 255-262 ◽  
Author(s):  
M A Kowalska ◽  
A K Rao ◽  
J Disa
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Inhibitory Effect ◽  
Irreversible Damage ◽  
Fura 2 ◽  
Messenger Molecules ◽  
Thromboxane Production ◽  
High Concentrations ◽  
Stimulation Of

1. Exposure of platelets to exogenous arachidonic acid results in aggregation and secretion, which are inhibited at high arachidonate concentrations. The mechanisms for this have not been elucidated fully. In our studies in platelet suspensions, peak aggregation and secretion occurred at 2-5 microM-sodium arachidonate, with complete inhibition around 25 microM. 2. In platelets loaded with quin2 or fura-2, the cytoplasmic Ca2+ concentration, [Ca2+]i, rose in the presence of 1 mM-CaCl2 from 60-80 nM to 300-500 nM at 2-5 microM-arachidonate, followed by inhibition to basal values at 25-50 microM. Thromboxane production was not inhibited at 25 microM-arachidonate. Cyclic AMP increased in the presence of theophylline, from 3.5 pmol/10(8) platelets in unexposed platelets to 8 pmol/10(8) platelets at 50 microM-arachidonate; all platelet responses were inhibited with doubling of cyclic AMP contents. 3. The adenylate cyclase inhibitor 2′,5′-dideoxyadenosine attenuated the inhibitory effect of arachidonate, suggesting that it is mediated by increased platelet cyclic AMP and that it is unlikely to be due to irreversible damage to platelets. 4. Aspirin or the combined lipoxygenase/cyclo-oxygenase inhibitor BW 755C did not prevent the inhibition by arachidonate of either [Ca2+]i signals or aggregation induced by U46619. 5. Thus high arachidonate concentrations inhibit Ca2+ mobilization in platelets, and this is mediated by stimulation of adenylate cyclase. High arachidonate concentrations influence platelet responses by modulating intracellular concentrations of two key messenger molecules, cyclic AMP and Ca2+.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

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