Search PubMed⌕ Search

Biomedical subjects

M Deleers

Publications and source records attributed to M Deleers.

At least 37 records · Page 2Linked to original sources
PubMed1985

Nutrient-induced changes in the pH of pancreatic islet cells.

Fluorescein rapidly accumulates in rat pancreatic islets exposed to fluorescein diacetate. The influence of environmental agents upon cellular pH was examined in fluorescein-labelled islets by recording their fluorescence intensity at 520 nm after excitation at 490 and 435 nm, respectively. Glucose caused a rapid, sustained and dose-related increase in cellular pH. Another nutrient secretagogue, 2-ketoisocaproic acid, also increased cellular pH. The stimulation of islet cells by non-nutrient secretagogues, e.g. by glibenclamide or in response to an increase in extracellular K+ concentration, decreased cellular pH, indicating that the nutrient-induced increase in cellular pH is not merely a consequence of stimulated Ca2+ inflow and/or insulin release. In either the presence of amiloride or absence of bicarbonate, glucose decreased cellular pH. These results strongly suggest that the acidification of islet cells which can be expected from the increased metabolism of glucose in glucose-stimulated islets is normally masked and overcome by stimulation of such processes as Na+/H+ and HCO3-/Cl- exchange.

Animals↗
PubMed1985

Glucose increases cytosolic Ca2+ activity in pancreatic islet cells.

Isolated cells prepared from rat pancreatic islets were labelled with the tetraacetoxymethyl ester of the fluorescent Ca2+ indicator quin-2. An increase in the extracellular concentration of glucose provoked a rapid and sustained increase in the fluorescence of the labelled cells. This indicates that glucose increases cytosolic Ca2+ activity in pancreatic islet cells.

Aminoquinolines↗
PubMed1985

Cationic atmosphere and cation competition binding at negatively charged membranes: pathological implications of aluminum.

Binding of cations to membranes may be the basis for explaining some of the effects of several neurotoxic cations. The binding of Al3+ and the displacement of Ca2+ by Al3+ is studied with the aid of a simple mathematical approach described here and giving the same results when compared to the mathematical formalism described by Nir and Bentz. The method allows the simulation of membranes with low surface charge densities that are relevant for biochemical and pathological implications. Fluorescence quenching of the phospholipid analogue 1-palmitoyl-2-nitrobenzoxadiazol amino caproyl- phosphatidyl choline (C6-NBD-Ptd Cho) embedded in phosphatidyl serine membranes is used to determine the competition between calcium and aluminum for binding. The effect of aluminum in the presence of chelating agents is also studied by quenching experiments. Finally, inhibition of 45Ca2+ binding to phosphatidyl serine has also been investigated in a two-phase system.

Aluminum↗
PubMed1984

Effect of lipid composition changes on carbocyanine dye fluorescent response.

Egg yolk phosphatidyl choline liposomes containing variable amounts of phosphatidyl ethanolamine, phosphatidyl inositol or phosphatidyl serine demonstrated important variations in the fluorescence of 3.3' dipropylthiodicarbocyanine. When the membrane contained no cholesterol, fluorescence was not correlated with membrane fluidity as measured by diphenyl hexatriene polarization. Increasing cholesterol concentration in valinomycin containing liposome membranes decreased the potassium induced apparent membrane potential and prevented sorption of dye to the membrane. Discontinuity in the apparent potential occurred at 30 mol% cholesterol but could not be correlated with changes in microviscosity. These results indicate that great care should be taken when correlating rapid variations of fluorescence to changes in membrane potential. We propose that changes in phospholipid metabolism could well explain fluorescent changes when monitoring the fluorescence of cyanine dye molecules sorbed to biological membranes.

Benzothiazoles↗
PubMed1984

Metabolic and secretory effects of methylamine in pancreatic islets.

The metabolic and secretory effects of methylamine in rat pancreatic islets were investigated. Methylamine accumulated in islet cells, was incorporated into endogenous islet proteins, and inhibited the incorporation of [2,5-3H] histamine into either N,N-dimethylcasein or endogenous islet proteins. Methylamine (2 mM) did not affect the oxidation of glucose or endogenous nutrients or the intracellular pH in islet cells. Glucose did not affect the activity of transglutaminase in islet homogenates, the uptake of 14C-methylamine by intact islets or its incorporation into endogenous islet proteins. Methylamine inhibited insulin release evoked by glucose, other nutrient secretagogues, and non-nutrient insulinotropic agents such as L-arginine or gliclazide. The inhibitory effect of methylamine upon insulin release was diminished in the presence of cytochalasin B or at low extracellular pH. Methylamine retarded the conversion of proinsulin to insulin. Trimethylamine (0.7 mM) was more efficiently taken up by islet cells than methylamine (2.0 mM), and yet caused only a modest inhibition of insulin release. These findings suggest that methylamine interferes with a late step in the secretory sequence, possibly by inhibiting the access of secretory granules to their exocytotic site.

Acyltransferases↗
PubMed1984

Binding of hypoglycaemic sulphonylureas to an artificial phospholipid bilayer.

Hypoglycaemic sulphonylureas bind to multilamellar liposomes formed of egg yolk phosphatidylcholine. In this artificial model, both specific and non-specific components of the binding phenomenon can be characterized by the same criteria as those used in studies performed with natural membranes. The relative ability of distinct sulphonylureas to inhibit the binding of 3H-glibenclamide or 3H-gliquidone to the liposomes parallels their relative potency as insulin secretagogues. It is proposed that the insertion of hypoglycaemic sulphonylureas into the phospholipid domain of the B cell membrane could represent a primary event in the mechanism by which these agents stimulate insulin release.

Glyburide↗
PubMed1984

Sequence of ionophore conformational changes induced by a simulated membrane/water interface.

We demonstrate how the progressive passage through an interface simulated by a linear increase in dielectric constant may mediate a reversible transconformation of Na+/X537A (lasalocid A) from a cyclic to an extended structure. During the passage through the interface, the complex adopts progressively a more extended conformation favorable to the Na+ complexation or decomplexation at the interface.

Energy Transfer↗
PubMed1984

Methylamines and islet function: cationic aspects.

Methylamine (2 to 10 mM) caused a dose-related inhibition of insulin release evoked in rat pancreatic islets by nutrient or non nutrient secretagogues. Trimethylamine exerted comparable effects upon insulin release. Methylamine (2 mM) inhibited insulin secretion but failed to affect 45Ca uptake and efflux in response to a rise in extracellular K+ concentration, suggesting that methylamine acts, to a certain extent at least, at a distal site in the secretory sequence. Methylamine, however, also exerted untoward ionic effects. First, methylamine (2 to 10 mM) apparently caused a dose-related increase in cellular pH. Second, methylamine (2mM) augmented 86Rb outflow from islets perifused either in the absence or presence of glucose or gliclazide, and inhibited Ca2+ inflow (as judged from the net uptake or efflux of 45Ca) in islets stimulated by D-glucose, L-leucine or 2-ketoisocaproate. This multiplicity of ionic and other effects may account for the fact that, in the presence of distinct secretagogues, the secretory process appeared more or less sensitive towards methylamine, depending on the relative importance of changes in cellular pH, K+ permeability and intracellular Ca2+ distribution as determinants of the secretory response.

Acyltransferases↗
PubMed1984

Conformational analysis of 6-cis- and 6-trans-leukotriene B4-calcium complexes.

We present a computational description of the conformation of a pair of two isomeric molecules (6-cis-and 6-trans-leukotriene B4) forming a complex with one calcium ion. Our theoretical prediction of the membrane-water interface conformation and of the bulk lipid phase conformation of the two different isomeric complexes are in excellent agreement with experimental data on the leukotriene-mediated calcium ionophoresis in liposomes. The two isomers lead to vastly different conformations in the presence of Ca2+, and the most probable conformation of the permeant species shows a globular conformation able to cross a lipid membrane.

Calcium↗
PubMed1984

Effects of cations, ionophores and hypoglycemic sulfonylureas on the fluorescence of fluorescein-labelled pancreatic islets.

The stimulation of Ca2+ inflow into pancreatic islet cells resulting from either an increase in extracellular K+ (from 5 to 37 mM) or Ca2+ (from 1 to 20 mM) concentration or the administration of tolbutamide, glibenclamide and the ionophores A23187 or X537A resulted in an apparent fall of cellular pH as judged from the fluorescence of islets prelabelled with fluorescein diacetate. In all cases, the decrease in pH was abolished when the experiments were repeated in the absence of extracellular Ca2+. These results suggest that the cytosolic concentration of Ca2+ may affect the pH of islet cells, possibly by displacing H+ from intracellular binding sites.

Animals↗
PubMed1983

Localization in diphtheria toxin fragment B of a region that induces pore formation in planar lipid bilayers at low pH.

Like diphtheria toxin and the N-terminal (Mr 23 000) region of fragment B, CB1 (Mr 13 000), the cyanogen bromide peptide located in the middle region of fragment B is able to induce pore formation in lipid bilayer membrane at low pH. These two peptides (Mr 23 000 and 13 000) share a common segment (Mr 6300) containing the predicted amphipathic, alpha-helical, transverse lipid-associating domain (Mr 2750) of fragment B [J. Cell Biol. (1980) 87, 837-840]. Therefore, we postulated this domain to be responsible for the pore formation ability of diphtheria toxin [Proc. Natl. Acad. Sci. USA (1981) 78, 172-176]. A relationship between the pH dependency of pore formation and the presence of a cluster of prolines in the C-terminal region of CB1 is proposed.

Diphtheria Toxin↗
PubMed1983

Increase in CO3H- influx and cellular pH in glucose-stimulated pancreatic islets.

When rat islets are preincubated with fluorescein diacetate and examined in a spectrofluorometer, the intracellular pH rapidly increases by 0.21 pH units in response to a rise from 1.7-16.8 mM glucose. This coincides with a marked increase in 14CO3H- net uptake by the islets, suggesting that the glucose-induced increase in H+ generation rate is compensated for by stimulation of CO3H-/Cl- exchange.

Animals↗
PubMed1983

Conformational analysis of the calcium-antagonist gallopamil.

Conformational analysis of gallopamil was performed in order to gain insight into the molecular determinant of its calcium-antagonistic property. Whereas the neutral form of gallopamil was characterized by a single, largely predominant configuration, the protonated form of the drugs yielded several conformers, some of which were characterized by a readily accessible ionized site. The capacity of gallopamil to inhibit ionophore-mediated calcium translocation in a two-phase bulk system was inversely related to the pH of the aqueous phase. These findings indicate that the capacity of gallopamil to interfere with the transport of cations is critically dependent on the availability of a protonated configuration of the drug.

Calcimycin↗
PubMed1983

Calcium transport by a beta-diketone in model membranes.

The beta-diketone 1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dione (FOD) translocates calcium from an aqueous medium into an organic phase. FOD is less efficient than but acts synergistically with A23187 in causing calcium translocation. The FOD-mediated process of calcium translocation is inhibited by NaCl, although the translocation of sodium by FOD is two to three orders of magnitude lower than that of calcium, when expressed relative to the concentration of these cations in the aqueous medium. At pH 7.4, FOD mediates calcium exchange-diffusion in fluid liposomes as efficiently as A23187. The extent of exchange-diffusion depends on the rigidity and cholesterol content of the liposomes. Conformational analysis of the complex formed by two molecules of FOD and one calcium atom at a simulated membrane interface reveals the existence of several interconvertible, asymmetrical and more-or-less planar configurations. The efficiency of FOD-mediated calcium ionophoresis thus appears to be regulated in a multifactorial manner by such factors as the concentration of calcium and monovalent cations, chemical composition and fluidity of the membrane, availability of other ionophoretic molecules and spatial configuration of the calcium complex.

Calcium↗
PubMed1983

Conformational analysis of phorbol esters at a simulated membrane/water interface.

The conformation at a simulated membrane/water interface of four distinct phorbol esters, selected for their vastly different tumor-promoting potency, was predicted by a modification of the usual computing approach for the conformational analysis of macromolecules. In the modified procedure, the transfer energy of each part of the molecule in either a hydrophobic or hydrophilic domain was taken into account in order to define the orientation of the molecule at the simulated interface. The results of this study are compatible with known tensioactive properties of these phorbol esters, and may help to explain differences in their biological potency by the relative facility of their insertion in lipid bilayers.

Carcinogens↗
PubMed1983

Theoretical study on conformation-related activity of hypoglycemic sulfonylureas.

Theoretical conformational analysis has been carried out for different hypoglycemic sulfonylurea -Ca complexes. The formed complex has an hydrophobic external surface and a low amphiphilic character. Our results suggest that Calcium may effectively be transported across membranes of Langerhans B cells and that the different biological potencies of the drugs may be due in part to the shape of the different complexes.

Hypoglycemic Agents↗