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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 7 (1971), S. 339-348 
    ISSN: 1432-0428
    Schlagwort(e): Autoradiography ; 5-hydroxytryptamine ; 5-hydroxytryptophan ; monoamine oxidase inhibition ; mouse ; pancreatic islets ; reserpine ; ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Kurzfassung: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): B-cell ; B-cell granules ; DOPA ; dopamine ; electron microscopic autoradiography ; glibenclamide ; glucose ; insulin secretion ; isopropylnoradrenaline ; mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 20 (1981), S. 54-59 
    ISSN: 1432-0428
    Schlagwort(e): VIP ; secretin ; gastrin ; basal insulin secretion ; stimulated insulin secretion ; cholinergic stimulation ; β-adrenergic stimulation ; glucose stimulation ; in vivo ; mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The in vivo effects of vasoactive intestinal polypeptide (VIP), secretin and two different molecular forms of gastrin, gastrin 17 and pentagastrin, on basal and stimulated insulin secretion have been investigated in the mouse. All these peptides induced a moderate dose-dependent increase in basal insulin secretion. The different polypeptides showed complex effects on insulin release stimulated by glucose, the cholinergic agonist carbachol or the β adrenergic agonist L-isopropylnoradrenaline (LIPNA), these effects being dependent on the nature of the secretagogue. VIP and secretin both potentiated glucose-induced insulin release. Secretin inhibited insulin secretion induced by carbachol and LIPNA, whereas VIP potentiated L-IPNA-induced insulin secretion and had no influence on the effect of carbachol. Gastrin 17 and pentagastrin did not affect glucose- or carbachol-induced insulin release, whereas they inhibited L-IPNA-induced insulin secretion. The results suggest that VIP, secretin and gastrin display their effects on insulin secretion through different mechanisms. The results indirectly suggest the existence of separate insulin secretory pathways which operate differently, or at least partly differently, after glucose stimulation, cholinergic stimulation, and β-adrenergic stimulation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 21 (1981), S. 54-59 
    ISSN: 1432-0428
    Schlagwort(e): VIP ; secretin ; gastrin ; basal insulin secretion ; stimulated insulin secretion ; cholinergic stimulation ; β-adrenergic stimulation ; glucose stimulation ; in vivo ; mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The in vivo effects of vasoactive intestinal polypeptide (VIP), secretin and two different molecular forms of gastrin, gastrin 17 and pentagastrin, on basal and stimulated insulin secretion have been investigated in the mouse. All these peptides induced a moderate dose-dependent increase in basal insulin secretion. The different polypeptides showed complex effects on insulin release stimulated by glucose, the cholinergic agonist carbachol or theβ-adrenergic agonist L-isopropylnoradrenaline (L-IPNA), these effects being dependent on the nature of the secretagogue. VIP and secretin both potentiated glucose-induced insulin release. Secretin inhibited insulin secretion induced by carbachol and L-IPNA, whereas VIP potentiated L-IPNA-induced insulin secretion and had no influence on the effect of carbachol. Gastrin 17 and pentagastrin did not affect glucose- or carbachol-induced insulin release, whereas they inhibited L-IPNA-induced insulin secretion. The results suggest that VIP, secretin and gastrin display their effects on insulin secretion through different mechanisms. The results indirectly suggest the existence of separate insulin secretory pathways which operate differently, or at least partly differently, after glucose stimulation, cholinergic stimulation, andβ-adrenergic stimulation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 22 (1982), S. 258-263 
    ISSN: 1432-0428
    Schlagwort(e): Plasma glucagon ; mice ; muscular dystrophy ; gel filtration ; immunoglobulins ; glucose ; insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The present investigation was undertaken to determine and characterize glucagon immunoreactivity in plasma from normal NMRI mice and from dystrophic mice and their unaffected littermates of the 129/ReJ strain. Very young dystrophic mice (6 weeks old) displayed much higher basal levels of plasma glucagon immunoreactivity than normal mice. In contrast, plasma concentrations of insulin and glucose were lower in these dystrophic mice than in normal NMRI mice. The plasma glucagon levels declined with age in both strains during the time-period studied (1.5–5 months). Gel filtration of plasma from dystrophic as well as normal mice on Sephadex G-200 revealed that a large part of the total glucagon immunoreactivity was eluted in fractions containing the immunoglobulins. The amount of the ‘true’ glucagon part was lower in plasma from normal mice (about 0.2 μg/l) than in plasma from mice of the dystrophic strain (0.4–0.5 μg/l)). This finding was indirectly corroborated by the observation that a large intravenous glucose load decreased plasma glucagon by approximately 0.2 μg/l in the non-dystrophic NMRI strain and by about 0.4–0.6 μg/l in the dystrophic strain. Thus, the ability of glucose to suppress glucagon secretion appeared unaffected in the dystrophic mice. Glucose-induced insulin release, however, was considerably impaired in these animals. It is concluded that mice of the dystrophic 129/ReJ strain have higher plasma levels of ‘true’ glucagon than mice of the non-dystrophic NMRI strain. Whether the abnormally high plasma glucagon levels in the dystrophic strain, particularly in very young dystrophic mice, might contribute to the development of the muscular dystrophy remains to be elucidated.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 7 (1971), S. 414-422 
    ISSN: 1432-0428
    Schlagwort(e): 5-hydroxytryptamine ; 5-hydroxytryptophan ; monoamine oxidase inhibition ; decarboxylase inhibition ; glucose ; glibenclamide ; isopropylnoradrenaline ; alloxan diabetes ; mouse ; blood glucose ; immunoreactive insulin ; tissue glycogen ; hypoglycaemia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Kurzfassung: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 403-408 
    ISSN: 1432-1041
    Schlagwort(e): glibenclamide ; diabetes ; insulin ; kinetics ; blood glucose ; relationship to meals ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In an attempt to assess whether intake of glibenclamide before meals would improve its therapeutic capacity, the present investigation compared the effect of glibenclamide 2.5mg t.i.d. given before and together with meals. In addition, these effects were compared with that of glibenclamide given as a single morning dose of 7.5mg. The subjects studied were six Type 2 diabetics not previously exposed to sulphonylurea drugs. Irrespective of dosage and mode of administration, addition of glibenclamide to a standardized breakfast, lunch and dinner enhanced plasma IRI concentrations and reduced blood glucose concentrations as compared to administration of meals without the drug. The different modes of glibenclamide administration did not differ significantly with respect to IRI responses. However, the blood glucose reduction after breakfast was significantly greater when glibenclaimde 2.5mg had been given before the meal than when 2.5 or 7.5mg were given with the meal; a similar, but non-significant tendency was observed after lunch; no consistent difference was seen after dinner. Food intake did not affect glibenclamide kinetics. It appears that administration of glibenclamide 2.5mg before breakfast improved glucose utilization following the breakfast load, due to earlier attainment of an effective concentration of glibenclamide.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 8
    ISSN: 1432-0428
    Schlagwort(e): Blood glucose ; glibenclamide ; immunoreactive insulin ; isopropylnoradrenaline ; mouse ; pancreatic islets ; ultrastructure ; vinblastine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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