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Biomedical subjects

J Sehlin

Publications and source records attributed to J Sehlin.

At least 91 records · Page 5Linked to original sources
PubMed1982

5-hydroxytryptamine stimulates 86Rb+ efflux from pancreatic beta-cells.

The effects of 5-hydroxytryptamine and 5-hydroxytryptophan on 86Rb+ efflux from prelabelled ob/ob-mouse islets were studied to better understand the cellular mechanisms underlying the effects of 5-hydroxytryptamine and 5-hydroxytryptophan on insulin release. 5-Hydroxytryptophan (4 mM) had no effect on 86Rb+ efflux either at a low (3mM) or at a high (20 mM) D-glucose concentration, whereas 5-hydroxytryptamine (4 mM) stimulated 86Rb+ efflux at both glucose concentrations. These results indicate that 5-hydroxytryptamine may reduce glucose-induced insulin release by inhibiting early steps in the beta-cell stimulus-secretion coupling.

5-Hydroxytryptophan↗
PubMed1982

Bromocriptine and insulin secretion.

The dopaminergic drug bromocriptine inhibited the release of insulin from isolated mouse pancreatic islets. The effect was counteracted by haloperidol or pimozide. It is suggested that insulin release may be inhibited through activation of D-2 dopaminergic receptors in the pancreatic beta-cells.

Animals↗
PubMed1981

Potassium-stimulated 45Ca2+ uptake by subcellular particles of pancreatic beta-cells.

Accumulation of 45Ca2+ by a microsomal fraction from pancreatic beta-cells of obese-hyperglycemic (ob/ob) mice was stimulated by Mg2+ in a concentration-dependent manner when 2 mM ATP was present. Maximum effect was reached at 2 mM Mg2+. Increasing the Na+ concentration from 20 to 115 mM had no significant effect, but K+ (10-123 mM) stimulated 45Ca2+ accumulation markedly when tested in the presence of 2 mM Mg2+. This effect was not due to changes of osmolarity, ionic strength, or the concentration of Cl-. Stimulation by K+ was drastically reduced on omission of Mg2+ from the incubation medium. K+ did not significantly affect 45Ca2+ uptake by a mitochondria-rich fraction of ob/ob mouse islets. It is suggested that K+ may be involved in modifying the subcellular distribution of calcium ions in pancreatic beta-cells.

Animals↗
PubMed1980

Influence of the murine diabetes gene on rubidium ion efflux from perifused islets.

Islets from diabetic C57BL/KsJ db/db mice and normal C57BL/KsJ +/+ mice were loaded with 86Rb+ and micro-perfused with nonradioactive medium for 25 min. The appearance of 86Rb+ in the effluent could be described as the sum of two exponential functions with difference proportionality constants. The rapid efflux component may have represented washout from the extracellular space, and had about the same proportionality constant in normal and diabetic mice. The slow efflux component probably reflected efflux across the islet cell plasma membranes. At 3 mmol/l D-glucose in the medium, the slow efflux was significantly retarded in diabetic as compared with normal mice. In normal mice, but not in diabetics, 20 mmol/l D-glucose inhibited the slow efflux component. It is concluded that the basal K+ permeability is decreased in KsJ db/db mouse islet cells, and that this abnormality may explain their persistant depolarization at low glucose concentrations.

Animals↗
PubMed1980

Characteristics of 5-hydroxytryptamine transport in pancreatic islets.

1 Transmembrane transport of 3H-labelled 5-hydroxytryptamine (5-HT) by isolated pancreatic islets of non-inbred ob/ob mice was studied. 2 5-HT was vigorously accumulated in a temperature-dependent way by the islet cells. 3 Studies of the concentration-dependence of [3H]-5-HT uptake revealed complex kinetics with one component being saturated at 1 to 3 microM 5-HT (apparent association constant 0.6 x 10(6) M(-1) and the other non-saturated up to 1 mM 5-HT. 4 The saturable uptake was inhibited by Na+-deficiency and metabolic poisoning with 2,4-dinitrophenol and antimycin A, whereas the non-saturable component was not affected. 5 Omission of K+, Ca2+ or Mg2+ did not affect the uptake rate. 6 It is concluded that 5-HT is taken up by pancreatic beta-cells by mechanisms very similar to those observed in thrombocytes and neurones.

Animals↗
PubMed1980

Effects of acetylcholine on ion fluxes and chlorotetracycline fluorescence in pancreatic islets.

1. Acetylcholine potentiated glucose-stimulated insulin release from ob/ob-mouse islets in salt-balanced bicarbonate buffer and to a lesser extent in Tris buffer; basal insulin release at 3 mM-D-glucose was not affected. Potentiation required the presence of Ca(2+).2. In bicarbonate buffer, ACh stimulated the islet uptake of (45)Ca(2+) at 3 mM-glucose but not significantly at 11 mM; no effect was seen in Tris buffer.3. At 11 mM-glucose, ACh increased the fluorescence from Ca(2+)-chlorotetracycline in dispersed islet cells; the effect was inhibited by atropine.4. At both 3 and 11 mM-glucose, ACh stimulated the islet uptake of (22)Na(+) in 60 min. At 11 mM-glucose, (22)Na(+) uptake in 5 min was also enhanced significantly, and this effect was inhibited by atropine.5. At 3 mM-glucose, ACh probably stimulated the islet uptake of (86)Rb(+) in 10 min.6. ACh had no effect on (36)Cl(-) retention at 3 or 11 mM-glucose, or on the oxidation of D-[U-(14)C]glucose (11 mM).7. The insulin secretory potentiator, ACh, does not act by accelerating glucose oxidation and does not induce the same ionic effects as the secretory initiator, D-glucose. Increased Na(+) permeability and altered interaction of Ca(2+) with the plasma membrane may play roles in the cholinergic depolarization of beta-cells and potentiation of insulin release.

Acetylcholine↗
PubMed1980

Defective regulation of Cl- permeability in islets of diabetic mice [C57BL/KsJ(db/db)].

Efflux of 36Cl- from prelabeled, collagenase-isolated islets of noninbred ob/ob mice, inbred diabetic [C57BL/KsJ(db/db)] mice, and nondiabetic [C57BL/KsJ(+/+)] mice was studied by nonrecirculating perifusion. Islets of both ob/ob mice and nondiabetic KsJ mice showed similar rates of basal 36Cl- efflux, D-glucose stimulation of the 36Cl- efflux, and net uptake of 36Cl- at apparent isotope equilibrium. The 36Cl- efflux in islets from both young and old KsJ-db/db mice was almost insensitive to the D-glucose concentration. The basal rate of 36Cl- efflux in islets from young and old db/db mice was increased, indicating an abnormally high Cl- permeability. It is suggested that the defective regulation of the membrane potential in B-cells from [C57BL/KsJ(db/db)] mice may at least partly be caused by a db-mediated defect in the regulation of Cl- permeability.

Aging↗
PubMed1980

Cytotoxic activation of complement by mouse pancreatic islet cells.

Human serum, or serum proteins excluded by Sephadex G-25, irreversibly inhibited the ability of mouse pancreatic islet cells to accumulate Rb+. The same treatment reduced the capacity of serum to subsequently inhibit Rb+ uptake by fresh islet cells or to lyse sensibilized sheep erythrocytes. Serum-treated islet cells exhibited electron microscopic signs of damage, including ruptures of the plasma membrane, swelling of mitochondria, and reduced electron density of the cytoplasmic ground substance. Serum induced a prompt insulin release, which was not inhibited by epinephrine. The serum effects were prevented by mild heating (50 degrees C or 56 degrees C, 30 min) but not by treating serum with 10 mM EGTA and 10 mM MgCl2, or with soybean trypsin inhibitor. Inhibition of Rb+ accumulation in response to human serum was also observed with dispersed mouse exocrine pancrease, liver, and spleen cells but not with whole islets. Homologous mouse serum had no effect on mouse liver or spleen cells but significantly decreased the Rb+ uptake by mouse islet cells. Autologous serum had no noticeable effect. It is suggested that mouse islet cells can activate complement via the alternative pathway and that triggering of this pathway is controlled by cellular discriminators of species, organ, and self.

Animals↗
PubMed1980

Cation-activated phosphatase activities in islet cell plasma membrane preparations.

Pancreatic islets from rats or ob/ob mice were homogenized and fractionated either by a two-step or one-step sucrose gradient centrifugation. A plasma membrane enriched fraction was obtained at a sucrose density of about 1.10. The distribution of the plasma membrane probe 125I-wheat germ agglutinin was parallel to that of other plasma membrane markers. Hydrolysis of Mg-ATP-gamma-3Pp in rat islet membranes was of high specific activity, but was little affected by K+ and/or Na+. K+-activated, ouabain-sensitive phosphatase activities were, on the other hand, readily demonstrated in both rat and ob/ob mouse islet membranes. The K+-activated hydrolysis of organophosphate indicators were markedly inhibited by ATP. The binding of 45Ca2+ to mouse islet plasma membranes was increased by ATP. Cation transport and the interaction of Ca2+ with the islet cell plasma membrane may be dependent on phosphoryl-transfer reactions with ATP as the physiological substrate.

Adenosine Triphosphate↗
PubMed1979

Effects of glucose, chloromercuribenzene-p-sulphonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid on phosphate efflux from pancreatic islets.

Collagenase-isolated pancreatic islets of non-inbred ob/ob mice, containing more than 90% beta-cells, were labelled with radioactive orthophosphate (32P or 33P) and then subjected to non-recirculating perifusion. The basal D-glucose concentration in the perifusion medium was 2.8 mM. When the concentration was suddenly raised to 5.6, 8.3 or 16.7 mM, D-glucose promptly elicited a transient and dose-dependent release of radiophosphate. In the presence of 2.8 mM D-glucose, 0.1 mM of the poorly permeating sulphydryl blocker, chloromercuribenzene-p-sulphonic acid, also evoked a phosphate flush resembling the one induced by D-glucose. The basal radiophosphate release was partially inhibited by 1 mM 4-acetamido-4-'-isothiocyanostilbene-2,2'-disulphonic acid. However, the phosphate flush induced by 16.7 mM D-glucose was not noticeably inhibited by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid. It is concluded that the phosphate flush emanates from beta-cells and that membrane sulphydryl groups may participate in its regulation. Although at least the basal phosphate release may in part represent transmembrane transport through 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid-sensitive anion channels, other mechanisms are also likely to participate in the glucose-induced phosphate flush.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1979

Superoxide dismutase, catalase and scavengers of hydroxyl radical protect against the toxic action of alloxan on pancreatic islet cells in vitro.

Experiments with isolated pancreatic islets or dispersed islet cells from non-inbred ob/ob mice were performed to test the hypothesis that free radicals, notably OH., mediate the diabetogenic toxicity of alloxan. Accumulation of 86Rb+ by whole islets and exclusion of Trypan Blue by dispersed cells were used as previously validated criteria of islet-cell viability. Alloxan alone drastically inhibited the Rb+ accumulation and significantly decreased the frequency of cells excluding Trypan Blue. Enzymic scavengers of O2.- and H2O2 or non-enzymic scavengers of OH. or singlet oxygen were added to the incubation medium and tested for their ability to protect against these effects of alloxan. Superoxide dismutase, catalase, dimethyl sulphoxide, benzoate, and mannitol counteracted the effects of alloxan in both cytotoxicity assays. Significant protection of the Rb+-accumulating capacity was also afforded by butanol, caffeine, theophylline, NADH, NADPH and, to a small extent, NAD+. Urea has a poor affinity for OH. and did not protect against alloxan. No effect was obtained with the singlet-oxygen scavenger, histidine. Except for the protection by NADH and NADPH, which may be due to a direct reaction with alloxan in the medium, the results strongly support the hypothesis. beta-Cells may be particularly vulnerable to alloxan because their metabolic specialization facilitates reduction of the drug and perhaps of other substrates for O2.--yielding redox cycles.

Alloxan↗