Search PubMed⌕ Search

Biomedical subjects

E Gylfe

Publications and source records attributed to E Gylfe.

At least 145 records · Page 8Linked to original sources
PubMed1982

Amounts and distribution of intracellular magnesium and calcium in pancreatic beta-cells.

beta-Cell-rich pancreatic islets were incubated for 60-120 min in the presence of 1 mM or 20 mM glucose and analysed with regard to their contents of magnesium and calcium and how these elements were distributed among subcellular fractions. The islets contained 42 mmol magnesium per kg protein with as much as 70 mmol per kg protein in the microsomal fraction. Both the total amount and intracellular distribution of magnesium remained unaffected after raising the glucose concentration of the incubation medium. The islet content of calcium was twice as high as that of magnesium, the mitochondria and secretory granules accounting for most of the calcium in the sedimentable fractions. In both organelles a substantial fraction of calcium was exchangeable as indicated from the incorporation of 45Ca during 90 min of incubation of the islets. When raising the glucose concentration to 20 mM the percentage exchange of calcium increased from 10 to 27 in the mitochondria and from 13 to 28 in the secretory granules. The glucose stimulation of 45Ca uptake was not associated with a statistically significant increase in the total amounts of calcium. However, in addition to stimulating calcium/calcium exchange, it cannot be excluded that glucose also induces a net accumulation of intracellular calcium in the beta-cells.

Animals↗
PubMed1982

Evidence for a slowly exchangeable pool of calcium in the pancreatic beta cell plasma membrane.

1. Exposure to media deprived of Ca2+ resulted in prompt and transient stimulation of 45Ca efflux from beta cell-rich pancreatic islets microdissected from ob/ob-mice and to some extent also from the isolated neurohypophysis. 2. Particular high efflux rates were reached when the Ca2+-deficient medium contained EGTA, but there was no effect of the chelator on the total amount of radioactivity mobilized from the islets. 3. The removal of extracellular Ca2+ was less effective in promoting the 45Ca efflux in the absence of Na+ and no stimulatory response was seen in the presence of 1 mM-La3+. 4. The 45Ca washout was stimulated whether or not the media used for the loading or subsequent perifusion of the islets were supplemented with 20 mM-D-glucose. However, there was no response to a second exposure to a Ca2+-deficient medium even subsequent to redistribution of intracellular calcium induced by temporary lowering of the temperature. 5. It is suggested that the islet 45Ca released by the removal of extracellular Ca2+ originates from a distinct plasma membrane pool which is exchanged slowly compared to most of the calcium at the beta cell periphery.

Animals↗
PubMed1982

Is Mg2+ important for the secretory function of the pancreatic beta-cells?

The interactions between Mg2+ and Ca2+ and the total content of magnesium were studied in beta-cell-rich pancreatic islets from ob/ob mice. High concentrations of Mg2+ inhibited basal intracellular 45Ca net uptake as well as that stimulated by K+ depolarization or Na+ omission, suggesting that Ca2+ and Mg2+ can compete for both the voltage-dependent Ca2+ and the Na+ channels. The magnesium content of the islets was remarkably stable being affected only under extreme conditions. It is suggested that the physiological stimulation of insulin secretion does not depend on dynamic fluctuations of magnesium metabolism.

Animals↗
PubMed1982

The insulin-releasing activity of the tropical plant momordica charantia.

An aqueous extract from the unripe fruits of the tropical plant Momordica charantia was found to be a potent stimulator of insulin release from beta-cell-rich pancreatic islets isolated from obese-hyperglycemic mice. The stimulation of insulin release was partially reversible. It differed from that of D-glucose and other commonly employed insulin secretagogues in not being suppressed by L-epinephrine and in even being potentiated by the removal of Ca2+. This anomalous behaviour was not associated with general effects on the metabolism of the beta-cells as indicated by an unaltered oxidation of D-glucose. Studies of 45Ca fluxes suggest that the insulin-releasing action is the result of perturbations of membrane functions. In support for the idea of direct effects on membrane lipids, the action of the extract was found to mimic that of saponin in inhibiting the Ca2+/H+ exchange mediated by the ionophore A23187 in isolated chromaffin granules and release Ca2+ from preloaded liposomes.

Animals↗
PubMed1982

Lack of Ca2+ ionophoretic activity of hypoglycemic sulfonylureas in excitable cells and isolated secretory granules.

Beta-Cell-rich pancreatic islets, neurohypophyses, and adrenal medullae were used for exploring whether hypoglycemic sulfonylureas exhibit Ca2+ ionophoretic properties. Exposure of these excitable organs to depolarizing concentrations of K+ resulted in stimulation both of 45Ca uptake and efflux. Although tolbutamide does not bind preferentially to pancreatic islets, this sulfonylurea was specific in stimulating the fluxes of 45Ca in these endocrine specimens. A chromaffin granule preparation was used for studies of both the net transport of Ca2+ with the metallochromic indicator arsenazo III and the proton concentration gradient (delta pH) with the fluorescent probe 9-aminoacridine. Even at high concentrations, tolbutamide and glibenclamide did not mediate Ca2+ -H+ exchange diffusion whether or not the granules were made permeable to protons by the addition of the protonophore carbonyl cyanide rho-trifluoromethoxyphenylhydrazone, nor did the sulfonylureas affect Ca2+ -H+ exchange diffusion induced by the addition of A-23187. The data indicate that the Ca2+ fluxes associated with sulfonylurea-stimulated insulin secretion do not result from the Ca2+ -ionophoretic properties of the drugs but rather reflect depolarization of the beta-cells.

Animals↗
PubMed1981

Influence of external calcium ions on labelled calcium efflux from pancreatic beta-cells and insulin granules in mice.

Addition of Ca2+ to a glucose-free perifusion medium stimulated the efflux of 45Ca from prelabelled pancreatic islets isolated from ob/ob-mice. This effect differed from that of glucose in being transient, markedly stimulated by previous exposure to a Ca2+-deficient medium and resulting in mobilization also of substantial amounts of 45Ca incorporated in the absence of glucose. The glucose action on 45Ca efflux reflected the balance between inhibitory and stimulatory components which differed with respect to their chronological order and sensitivity to glucose. The magnitude of the stimulatory phase was related linearly to the extracellular concentration of Ca2+ up to 2.40 mM. The efflux of 45Ca from isolated secretory granules was stimulated by Mg-ATP. The latter made the 45Ca efflux from the granules sensitive to Ca2+; significant stimulation being seen when increasing the medium Ca2+ from 0.1 to 10 microM. The results support the concept of an efficient Ca/Ca exchange mechanism in the depolarized beta-cells, emphasizing a role for the secretory granules in this process.

Animals↗
PubMed1981

Thulium binding to the pancreatic beta-cell membrane.

Radioactive thulium (171Tm) was used to probe cation-binding sites in the plasma membrane of beta-cell-rich pancreatic islets microdissected from noninbred ob/ob mice. Temporal studies revealed that 171Tm uptake was rapid, reaching isotopic equilibrium by 60 min. Analysis of the concentration dependence of 171Tm uptake revealed at least two components. At low 171Tm concentrations (0.003--0.18 micrometer), there was a saturable low capacity component, capable of accommodating less than 20 mumol/kg dry weight. At higher 171Tm concentrations (1.0--500 micrometers), a nonsaturable high capacity component capable of binding more than 100 mmol/kg dry weight was observed. 171Tm taken up at 0.18 micrometer exhibited a high degree of mobility. The uptake of 171Tm at this concentration was increased by incubation with chlorpromazine at concentrations known to increase the permeability of the beta-cell plasma membrane. At 0.18 micrometer, exposure to 20 mM D-glucose reduced 171Tm uptake compared with that in islets incubated in the absence of sugar or in the presence of sugars which lack stimulatory effects on insulin release. Such an effect was not observed at 125 micrometers, and none of the sugars influenced the 171Tm uptake of the exocrine pancreas. These data raise the possibility that cation-binding sites in the beta-cell plasma membrane are of physiological significance in the regulation of insulin secretion.

Animals↗
PubMed1981

Bo Hellman.

Explore the source record for details and available documents.

Endocrinology↗
PubMed1980

Calcium and pancreatic beta-cell function. 7. Evidence for cyclic AMP-induced translocation of intracellular calcium.

The effect of cyclic AMP on calcium movements in the pancreatic beta-cell was evaluated using an experimental approach based on in situ labelling of intracellular organelles of ob/ob-mouse islets with 45Ca. Whereas the glucose-stimulated 14Ca incorporation by mitochondria and secretory granules was increased under a condition known to reduce cyclic AMP (starvation), raised levels of this nucleotide (addition of 3-isobutyl-1-methylxanthine or N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate) reduced the mitochondrial accumulation of 45Ca. Conditions with increased cyclic AMP were associated with a stimulated efflux of 45Ca from the secretory granules but not from the mitochondria. The microsomal fraction differed from both the mitochondrial and secretory granule fractions by accumulating more 45Ca after the addition of 3-isobutyl-1-methylxanthine. The results suggest that cyclic AMP potentiates glucose-stimulaated insulin release by increasing cytoplasmic Ca2+ at the expense of the calcium taken up by the organelles of the pancreatic beta-cells.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Effects of metabolic inhibitors on the efflux of 5-hydroxytryptamine from pancreatic Beta-cells.

The influence of glucose and metabolic inhibitors on the efflux of tritiated 5-hydroxytryptamine (5-HT) was studied in perifused beta-cell-rich ob/ob mouse islets loaded with trace amounts of 3H-5-hydroxytryptophan. Glucose stimulated exocytotic release of 5-HT but the effect was rapidly inhibited by 2,4-dinitrophenol, antimycin A or N-ethylmalemide. This inhibition was followed by a marked stimulation of 5-HT efflux. The later phenomenon was reversible when 2,4-dinitrophenol was used by appeared irreversible with antimycin A or N-ethylmalemide. The results show that the maintenance of 5-HT within the beta-cell depends on energy. It is suggested that both inhibitory and stimulatory effects of 5-HT on insulin secretion depend on release of calcium from the secretory granules after short-circuiting a proton pump across the granule membrane.

Animals↗
PubMed1980

Calcium and pancreatic beta-cell function. IX. Demonstration of lanthanide-induced inhibition of insulin secretion independent of modifications in transmembrane Ca2+ fluxes.

beta-Cell-rich pancreatic islets were microdissected from noninbred ob/ob-mice and used to examine the mode of action of trivalent lanthanide ions on insulin secretion. La3+, Sm3+, and Tm3+ were equally effective inhibitors of basal and glucose-stimulated insulin release. As indicated by perifusion experiments with Tm3+, the inhibitory action was prompt, sustained, and readily reversible. Despite the similarities among the lanthanides in inhibiting insulin secretion, these cations differed considerably in their ability to impair transmembrane 45Ca fluxes. Using 10 different members of the lanthanide series, it was possible to demonstrate that their effectiveness to inhibit 45Ca uptake increased with ionic radius. La3+ markedly inhibited intracellular uptake and superficial binding of 45Ca at both 3 and 20 mM glucose. However, Tm3+ failed to affect intracellular 45Ca uptake and only reduced superficial binding of 45Ca at 3 mM glucose. In efflux experiments, Tm3+ did not affect basal or glucose-stimulated 45Ca washout from islets perifused with a medium containing 1.28 mM Ca2+. In a Ca2+-deficient medium, Tm3+ caused a slight transient increase, followed by reduction of 45Ca washout. However, when glucose was omitted, there was a prompt increase in the washout of radioactivity in the presence of Tm3+. Accordingly, the potent inhibitory action of Tm3+ on insulin secretion is not matched by changes in transmembrane Ca2+ fluxes. Since the lanthanides do not penetrate intracellularly, we propose the existence of cationic binding sites in the beta-cell plasma membrane with direct inhibitory effects on insulin secretion.

Animals↗
PubMed1980

Ca2+ transport in pancreatic beta-cells during glucose stimulation of insulin secretion.

The role of Ca2+ in the regulation of insulin secretion was evaluated using beta-cell-rich pancreatic islets isolated from ob/ob-mice. The glucose stimulation of the secretory activity is supposed to result from accumulation of Ca2+ in the submembrane cytoplasmic space. It is likely that this process reflects the balance between increased entry of Ca2+ into the beta-cells and an enhanced sequestration of Ca2+ in the organelle sinks. The proposed model can explain the cAMP potentiation of glucose-stimulated insulin release with suppression of the mitochondrial Ca2+ uptake. Furthermore, differences in the Ca2+ buffering capacity of the secretory granules may account for other characteristic features of glucose-stimulated insulin release, in particular its biphasic nature and sensitivity to suppression on withdrawal of nutrients.

Adenosine Triphosphate↗
PubMed1980

Calcium movements in relation to glucose-stimulated insulin secretion.

The influence of glucose on the beta-cell handling of Ca2+ was studied in pancreatic islets isolated from ob/ob mice. Glucose had both stimulatory and inhibitory effects on the washout of radioactivity from islets preloaded with 45Ca. Although the phenomenon of stimulation may be essentially associated with an increased turnover of 45Ca incorporated in response to glucose, the inhibitory effect might merely reflect a lowering of Ca2+ in the cytoplasm following from its accumulation into secretory granules and mitochondria. It is suggested that the Ca2+ uptake by the granules is mediated by an ATP-dependent proton gradient and that these organelles serve as a regulator of the cytoplasmic Ca2+ involved in stimulus-secretion coupling. Alterations in the beta-cell handling of Ca2+ may not only explain the role of glucose as an initiator of insulin release, but also the potentiation by cAMP of the action of glucose. The latter effect can tentatively be ascribed to an increase of cytoplasmic Ca2+ following cAMP-induced inhibition of the net Ca2+ uptake by mitochondria.

1-Methyl-3-isobutylxanthine↗