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  • 1
    ISSN: 1432-0428
    Keywords: B-cell ; B-cell granules ; DOPA ; dopamine ; electron microscopic autoradiography ; glibenclamide ; glucose ; insulin secretion ; isopropylnoradrenaline ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Accumulation and subcellular localization of dopamine (DA) in pancreatic B-cells and its effects on insulin secretion were investigated in mice following a single injection of L-3,4-dihydroxyphenyl-alanine (L-DOPA). Electron microscopic autoradiography showed that3H-DA formed from administered3H-DOPA was present over B-cells as well as over other types of islet cells. Pretreatment of the animals with a decarboxylase inhibitor greatly reduced the number of autoradiographic grains. In the B-cells the3H-DA-grains were associated with the secretory granules. The location of the label may suggest an incorporation in the periphery of the β-granule, rather than in the dense core, supposed to contain insulin. Accumulation of DA in the B-cells following L-DOPA administration was found to inhibit partially the insulin secretory response to different insulin secretagogues (glucose, glibenclamide and L-isopropylnoradrenaline (L-IPNA)). Treatment with monoamine oxidase inhibitor + L-DOPA induced an almost total suppression of L-IPNA-stimulated insulin secretion, whereas glucose-induced insulin release was still only partially inhibited. Pretreatment with a decarboxylase inhibitor abolished the effects of L-DOPA. It is suggested that intracellularly accumulated DA in the B-cell exerts an inhibitory action on insulin releasing mechanisms induced by different secretagogues and that this action might involve interference with a calcium translocation process at the level of the secretory granule.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 414-422 
    ISSN: 1432-0428
    Keywords: 5-hydroxytryptamine ; 5-hydroxytryptophan ; monoamine oxidase inhibition ; decarboxylase inhibition ; glucose ; glibenclamide ; isopropylnoradrenaline ; alloxan diabetes ; mouse ; blood glucose ; immunoreactive insulin ; tissue glycogen ; hypoglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez la souris normale a été étudiéein vivo la signification fonctionnelle du stockage de 5-hydroxytryptamine (5-HT) dans les cellules β du pancréas pour les mécanismes de la sécrétion d'insuline. Un traitement préalable des animaux avec leL-5-hydroxytryptophane (L-5-HTP) a nettement réduit la capacité de sécrétion d'insuline après stimulation par sulfonylurée. Cette inhibition de la sécrétion d'insuline pouvait être évitée par l'administration préalable d'un inhibiteur de décarboxylation d'acide aminé aromatique. D'un autre côté, le traitement préalable avec la nialamide, inhibiteur de la monoamine oxydase, réduisait la sécrétion d'insuline provoquée par sulfonylurée. Le traitement combiné avec la nialamide et leL-5-HTP n'a pas réduit davantage la réponse de l'insuline. Il a été trouvé que la sécrétion d'insuline provoquée par laL-isopropylnoradrénaline (L-IPNA) se réduisait également aprés l'administration préalable deL-5-HTP ou de nialamide, mais, contrairement à la réponse de l'insuline après sulfonylurée, la sécrétion d'insuline provoquée par l'IPNA pouvait être totalement supprimée par le traitement combiné avec la nialamide ou la pargyline et leL-5-HTP. La sécrétion d'insuline provoquée par le glucose n'était influencée de façon significative par aucun des traitements ci-dessus. Le taux basal d'insuline du plasma n'était pas affecté par l'injection deL-5-HTP et n'était pas réduit de façon certaine par le traitement combiné avec l'inhibiteur de la monamine oxydase et leL-5-HTP. Il a été trouvé que le traitement combiné avec l'inhibiteur de la monoamine oxydase et leL-5-HTP provoquait une hypoglycémie profonde à la fois chez la souris normale et chez la souris diabétique par l'alloxane. L'hypoglycémie était accompagnée d'un épuisement du contenu du glycogène du foie et des muscles. Il était possible d'éviter l'hypoglycémie par un traitement préalable avec un inhibiteur de décarboxylation d'acide aminé aromatique. Un traitement combiné avec la pargyline et la 5-HT a provoqué une nette hyperglycémie. — En conclusion: 1. Le taux intracellulaire de la 5-HT dans les cellulesβ du pancréas a la capacité de modifier les mécanismes de la sécrétion d'insuline. 2. L'action hypoglycémique des inhibiteurs de la monoamine oxydase est provoquée par l'accroissement du taux intracellulaire de 5-HT qui s'accompagne d'une nette augmentation de l'utilisation du glucose par les tissus.
    Abstract: Zusammenfassung Es wurde bei normalen Mäusenin vivo die funktionelle Bedeutung der Speicherung von 5-Hydroxytryptamin (5-HT) in den B-Zellen des Pankreas für die Mechanismen der Insulinsekretion untersucht. Eine Vorbehandlung der Tiere mitL-5 Hydroxytryptophan (L-5-HTP) verminderte deutlich die Insulinsekretion nach Stimulation mit Sulfonylharnstoff. Diese Hemmung der Insulinsekretion konnte durch vorherige Behandlung mit einem Hemmer der aromatischen Aminosäurendekarboxylase verhindert werden. Andererseits wurde die durch Sulfonylharnstoff bewirkte Insulinsekretion nach alleiniger Vorbehandlung mit dem Monoamino-oxidasehemmer Nialamid vermindert. Die kombinierte Behandlung mit Nialamid undL-5-HTP hat die Insulinantwort nicht weiter gemindert. Die durchL- Isopropylnoradrenalin (L-IPNA) bewirkte Insulinausschüttung wurde ebenfalls nach einer vorherigen Behandlung mitL-5-HTP oder Nialamid reduziert. Aber im Gegensatz zu der Insulinantwort nach Sulfonylharnstoff konnte die durch IPNA induzierte Insulinausschüttung völlig durch die kombinierte Behandlung mit Nialamid oder Pargylin plusL-5-HTP unterdrückt werden. Die durch Glucose herbeigeführte Insulinausschüttung wurde nicht wesentanimals lich durch eine der oben erwähnten Behandlungen verändert. Die basale Plasmainsulinkonzentration wurde durch dieL-5-HTP-Injektion nicht beeinflußt und war auch nicht wesentlich durch die kombinierte Behandlung mit dem Monoaminooxidasehemmer undL-5-HTP vermindert worden. — Die kombinierte Behandlung mit Monoaminooxidase-Inhibitoren undL-5-HTP erzeugte eine tiefe Hypoglykämie in normalen und alloxandiabetischen Mäusen. Der hypoglykämische Zustand wurde von einem Verschwinden des Leber- und Muskelglykogens begleitet. Die Hypoglykämie konnte durch eine Vorbehandlung mit einem Inhibitor der aromatischen Aminosäuredekarboxilation verhindert werden. Die kombinierte Behandlung mit Pargylin und 5-HT führte zu einer starken Hyperglykämie. — Daraus wurde geschlossen, 1. daß die intrazelluläre Konzentration von 5-HT in den B-Zellen des Pankreas die Fähigkeit besitzt, den Mechanismus der Insulinsekretion zu beeinflussen, 2. daß die hypoglykämische Wirkung der Monoaminooxidase-Inhibitoren durch eine erhöhte intrazelluläre 5-HT-Konzentration erzeugt wird, welche von einer stark erhöhten Glucoseutilisation der Gewebe begleitet wird.
    Notes: Summary The functional significance of 5-hydroxytryptamine (5-HT) storage in the pancreatic B cells for insulin secreting mechanisms was studied in normal micein vivo. Pretreatment of the animals withL-5-hydroxytryptophan (L-5-HTP) markedly decreased the insulin releasing capacity after sulphonylurea stimulation. This inhibition of insulin release could be abolished by previous administration of an inhibitor of aromatic amino acid decarboxylation. On the other hand, pretreatment with the monoamine oxidase inhibitor nialamide alone, decreased sulphonylurea-induced insulin release. The combined treatment with nialamide andL-5-HTP did not further decrease the insulin response. Insulin release induced byL-isopropylnoradrenaline (L-IPNA) was also found to diminish after previous administration ofL-5-HTP or nialamide; but, unlike the insulin response to sulphonylurea, insulin release induced by IPNA could be totally suppressed by the combined treatment of nialamide or pargyline andL-5-HTP. Insulin release induced by glucose was not significantly influenced with any of the above treatments. Basal levels of plasma insulin were not affected byL-5-HTP injection, and were not consistently diminished by the combined treatment with monoamine oxidase inhibitor andL-5-HTP. The combined treatment with monoamine oxidase inhibitors andL-5-HTP was found to elicit a profound hypoglycaemia in both normal and alloxan-diabetic mice. The hypoglycaemic condition was accompanied by exhaustion of liver and muscle glycogen. The hypoglycaemia could be abolished by previous treatment with an inhibitor of aromatic amino acid decarboxylation. Combined treatment with pargyline and 5-HT brought about a marked hyperglycaemia. It is concluded that: 1. intracellular levels of 5-HT in the pancreatic B cells possess the ability to modify insulin secreting mechanisms; and 2. the hypoglycaemic action of monoamine oxidase inhibitors is brought about by raised intracellular levels of 5-HT, which is accompanied by a markedly increased glucose utilization by the tissues.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 339-348 
    ISSN: 1432-0428
    Keywords: Autoradiography ; 5-hydroxytryptamine ; 5-hydroxytryptophan ; monoamine oxidase inhibition ; mouse ; pancreatic islets ; reserpine ; ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé En appliquant la technique autoradiographique, on a étudié la distribution cellulaire et subcellulaire de la radioactivité dans les îlots pancréatiques de la souris après une injection intra-veineuse de3H-5-hydroxytryptophane. Des grains d'argent autoradiographiques dont la plupart représentent probablement de la 5-hydroxytryptamine qui s'est formée à partir du précurseur marqué, sont apparus sur les cellules A2 et B, tandis que très peu de grains ont été trouvés sur les cellules A1 à chacun des examens (entre 20 min et 16 h) et de même après l'inhibition de la monoamine-oxidase. L'analyse quantitative des coupes autoradiographiques a révélé que la concentration de grains d'argent sur les granules spécifiques des cellules A2 et B était 5 à 10 fois plus élevée que sur les parties restantes de ces cellules. Sur les cellules A2 le nombre le plus élevé de grains a été noté 20 min après l'injection du marqueur et sur les cellules B une heure après cette injection. Au bout de 8 h, il n'apparaissait que très peu de grains d'argent sur les cellules des îlots, et plus aucun au bout de 16 h. L'inhibition de la monoamine-oxidase a provoqué une augmentation de la rétention de marqueur sur les cellules des îlots, plus prononcée sur les cellules A2. Un traitement préalable à la réserpine a supprimé cette réaction autoradiographique.
    Abstract: Zusammenfassung Mit Hilfe der Technik der Autoradiographie wurde die zelluläre und subzelluläre Verteilung der Radioaktivität nach intravenöser Applikation von3H-5-Hydroxytryptophan in den Pankreasinseln der Maus untersucht. Die autoradiographischen Silberkörner, welche zumeist 5-Hydroxytryptamin darstellen, das aus der radioaktiven Ausgangssubstanz gebildet worden war, erschienen über den A2 und B-Zellen, während nach jedem untersuchten Zeitintervall (20 min–16 Std) auch wenn die Monoamino-Oxidase gehemmt wurde, nur sehr wenige Körner über den A1-Zellen erschienen. Quantitative Untersuchungen der Autoradiographieschnitte zeigten, daß die Konzentration der Silberkörner über den spezifischen Granula der A2-Zellen und der B-Zellen etwa 5–10 mal höher als über den restlichen Teilen der Zellen war. In den A2-Zellen wurde die höchste Körnerkonzentration nach 20 min, in den B-Zellen 1 Std nach Injektion der markierten Substanz festgestellt. Nach 8 Std zeigten sich nur wenige, nach 16 Std keine Silberkörner mehr über den Inselzellen. Die Hemmung der Monoamino-Oxidase verursachte eine vermehrte Anreicherung von Radioaktivität über den Inselzellen, am meisten über den A2-Zellen. Eine Vorbehandlung mit Reserpin verhinderte die autoradiographische Darstellung.
    Notes: Summary By application of autoradiographic technique the cellular and subcellular distribution of radio-activity in mouse pancreatic islets was investigated following intravenous administration of3H-5-hydroxytryptophan. Autoradiographic silver grains, most of which probably represent 5-hydroxytryptamine formed from the labelled precursor, appeared over A2 and B cells, whereas very few grains were recorded over A1 cells at any time investigated (20 min–16 hours) and also when monoamine oxidase was inhibited. Quantitative analysis of autoradiographic sections revealed that the concentration of silver grains over the specific granules of A2 and B cells was 5–10 times higher than over the remaining parts of these cells. In A2 cells the highest grain count was recorded at 20 minutes, in B cells at 1 hour after the injection of label. After 8 hours very few, and after 16 hours no silver grains appeared over islet cells. Inhibition of monoamine oxidase caused an increased retention of label over islet cells, most pronounced over A2 cells. Pretreatment with reserpine abolished the autoradiographic reaction.
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  • 4
    ISSN: 1432-0428
    Keywords: Blood glucose ; glibenclamide ; immunoreactive insulin ; isopropylnoradrenaline ; mouse ; pancreatic islets ; ultrastructure ; vinblastine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell was studied in mice. Treatment with vinblastine (1.1 μmole/mouse) resulted in a 75% decrease of the amount of normal microtubules and the appearance of characteristic paracrystals. Basal plasma immunoreactive insulin levels were depressed to about 60% of the control level. The dose-response pattern for insulin release (first phase) following two chemically unrelated insulin secretagogues, the potent sulphonylurea derivative, glibenclamide, and the β-adrenergic agonist L-isopropylnoradrenaline, (L-IPNA), was tested with and without vinblastine pretreatment. The dose-response curves for L-IPNA-induced insulin release in vinblastine-treated and control animals did not deviate significantly from each other, whereas insulin release following glibenclamide was almost totally suppressed by vinblastine except at the lowest dose level. Injection of maximal doses of glibenclamide or L-IPNA did not alter the ultrastructural changes induced by vinblastine in the B-cells. It is suggested that the microtubular system of the B-cell might play a minor role for certain insulin-releasing processes and/or that vinblastine might have other important effects on the insulin secretory machinery.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 185 (1960), S. 465-466 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The mussels were harvested in Lake Mlaren and transported in lake water to the laboratory. The livers were excised and homogenized in ice-cold phosphate buffer (0-05 M, pH 7-8) in a Potter-El veh j em homogenizer. Methyl donors and homocysteine were added to the homogenate to give incubation ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Steroid Biochemistry 20 (1984), S. 1443 
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 18 (1953), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Clinical oral implants research 2 (1991), S. 0 
    ISSN: 1600-0501
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 7 clinically stable, “osseointegrated”, titanium implants, inserted in human jaws for l–16 years, were retrieved for morphological analysis of the bone-titanium interface, using 3 different preparation techniques. The bone-titanium interface varied as judged from light microscopy of ground sections. The threads of the implants were well filled 79–95% with dense lamellar bone as quantified with morphometry. A large fraction of the implant surface (56–85%) appeared to be in direct contact with the mineralized bone. In general, the non-boric areas consisted of pockets with osteocytes, bone marrow tissue and/or vessels. Sections were prepared for light microscopy and transmission electron microscopy using a fracture technique. where the implant was separated from the embedded tissue before sectioning, and an electropolishing technique, where the bulk part of the implant was electrochemically removed. In areas judged as direct mineralized bone-titanium contact in the light microscope. the interfacial structure varied at the ultrastructural level. In areas along the interface, unmineralized tissue was present either as a narrow 0.5–l μm wide zone containing collagen fibril or as deeper pockets containing osteocytes or vessels. In areas with mineralized bone contact. an amorphous granular layer (100–400 nm wide) with no mineral was observed in the innermost interface bordering the mineralized bone, with an electron-dense lamina limitans-like line (approximately 50 nm thick). It is concluded that the bone-titanium interface of the 7 clinically retrieved titanium oral implants examined in the present study bone was heterogenous. In areas of a direct mineralized bone-titanium contact at the ultrastructural level. mineralized bone reached close to the implant surface, but was separated by an amorphous layer. 1 being 100–400 nm thick.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of materials science 4 (1993), S. 240-250 
    ISSN: 1573-4838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: The tissue response to screw-shaped implants of commercially pure titanium was studied by light microscopy 3–180 days after insertion in the rabbit tibia. The implant site in the tibial metaphysis consisted mainly of cortical bone. Three days after implantation, osteoblasts, producing osteoid, were observed at the endosteal surface and elongated mesenchymal cells were present in the injury area. Some macrophages but rather few other inflammatory cells were identified. Multinuclear giant cells were in direct contact with the implant and formed an almost continuous layer along the surface from the 7th day. The number of giant cells decreased with time and with increased bone-titanium contact. Bone formation was never seen direct on the implant surface but was first observed at day 7 as a woven trabecular bone formed at the endosteal surface and extending towards the implant and as a solitary formation of woven bone close to the implant. The solitary bone matrix served as a base for surface osteoblasts which produced osteoid in a lamellar arrangement. With time the two types of newly formed bone fused and more bone filled the threads and became remodelled by bone remodelling units. Light microscopic morphometry in ground sections demonstrated that the bone/titanium contact and bone area in the threads increased with time up to 6 months after implantation
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of materials science 3 (1992), S. 262-271 
    ISSN: 1573-4838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The interface zone between cortical bone and threaded non-alloyed titanium implants inserted in the rabbit tibia for 12 months was examined by light and electron microscopy. The implants were removeden bloc with the perfusion-fixed surrounding bone and the undecalcified specimens were, after osmification, dehydrated and embedded in plastic resin (LR White). In ground sections (about 10 µm thick) cortical bone appeared to be in direct contact with the implant surface and the implants were thus “osseointegrated”. Sections for light microscopy (1 µm thick) and electron microscopy (40 nm to 0.5 µm) were prepared by using an electropolishing technique by which the bulk part of the metal was electrochemically removed and a fracture technique by which the implant was separated from the embedded tissue before sectioning. In the electropolished specimens an unmineralized zone, 2–10 µm wide, was observed at the interface. The interface zone contained osteoid-like tissue (densely packed collagen fibrils, osteocyte canaliculi) but in general no deposits of calcium mineral. This feature of the interface could not be observed in specimens prepared by the fracture technique, indicating that the electropolishing technique had induced serious artefacts, including decalcification of the interface bone. In sections prepared by the fracture technique, mineralized bone was present very close to the implant surface. No gradient of mineral was observed. A thin layer of amorphous material (100–200 nm wide) was present peripheral to the mineralized bone. An electron dense line about 100 nm wide was formed at the border between the mineralized bone and the amorphous layer. The dense layer had the same characteristics as the lamina limitans observed around osteocyte lacunae and canaliculi or the zone between areas of bone with different degree of mineralization. Our observations suggest that mineralized bone reached close to the surface of titanium implants inserted in the rabbit tibia for 12 months but that a direct contact is not established.
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