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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Acyl-amino-alcyl benzoic acid derivative ; hypoglycaemic agent ; insulin release ; pancreatic polypeptide ; glucagon ; somatostatin ; tolbutamide ; unanaesthetized dogs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effects of HB 699, a non-sulphonyl urea acyl-amino-alcyl benzoic acid derivative, were studied in unanaesthetized dogs. Changes in blood glucose and plasma insulin, glucagon, pancreatic polypeptide and somatostatin were measured after a single intravenous injection. HB 699 caused hypoglycaemia and stimulated insulin secretion in a dosedependent manner. The effects of HB 699 (40 mg/ kg) on pancreatic hormone secretion were compared to those of tolbutamide given at a dose (12 mg/kg) which induced a similar maximal hypoglycaemia. Both drugs caused a similar increase in insulin release (180±32% for tolbutamide and 240±41% for HB 699) lasting for approximately 1 hour. Despite hypoglycaemia, plasma glucagon concentrations were unaltered by either substance. HB 699 caused a marked increase in the secretion of pancreatic polypeptide (220±60% at 30 min) for up to 2 hours, whereas tolbutamide caused no significant change in plasma pancreatic polypeptide levels. In contrast, while tolbutamide caused a significant (45±12%) but short-lived increase in plasma somatostatin concentrations, HB 699 had no significant effect.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Benzothiadiazine analogue ; LN 5330 ; diazoxide ; glucagon ; insulin ; somatostatin secretion ; dog ; isolated perfused rat pancreas
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary LN 5330 is a new benzothiadiazine which is a structural analogue of diazoxide. Its effects in vivo were studied on blood glucose levels and insulin, glucagon and somatostatin secretion in normal dogs, and in vitro on glucagon and insulin secretion from the isolated perfused rat pancreas. The results were compared with those obtained with diazoxide at equimolar dose or concentration. In the normal anaesthetized dog having a T-shaped catheter inserted in the pancreaticoduodenal vein, the infusion of LN 5330 (87.8 μmol/kg for 20 min) induced (1) a progressive increase in blood glucose levels, (2) a rapid decrease in insulin and somatostatin output rate, (3) an immediate increase in pancreatic glucagon secretion, and (4) a delayed decrease of arterial blood pressure. The equimolar dose of diazoxide provoked the same effects on blood glucose levels, insulin and somatostatin output, but a marked decrease in glucagon output and in arterial blood pressure. In the isolated rat pancreas perfused with 8.3 mmol/l glucose, the infusion of LN 5330 (440 μmol/l for 30 min) induced a drastic fall in insulin and a rapid and persistent increase in glucagon output. This stimulatory effect on glucagon secretion was not found with diazoxide at equimolar concentration. These findings show that LN 5330 is a substance which is distinct from diazoxide and interesting because of its double action: inhibition of insulin secretion and stimulation of glucagon secretion.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Insulin secretionin vivo andin vitro ; hypoglycaemic sulphonamide ; oral antidiabetic substances ; RP 22410 ; tolbutamide ; insulin secretion stimulator ; islets of Langerhans ; islet development ; beta cells ; betacytotrophic action ; Glisoxepid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Résumé Le glisoxepid ou RP 22410 est un nouveau sulfonylurée hypoglycémiant très actif. Chez le chien normal éveillé, administré par voie intraveineuse, il est 81 ou 131 fois plus actif que le tolbutamide, suivant que les doses sont exprimées en poids ou en moles. Cette action hypoglycémiante ne se manifeste pas chez le chien totalement dépancréaté. — Ce produit stimule la sécrétion d'insuline.In vivo chez le chien anesthésié ou éveillé, l'action du produit (que celui-ci soit administré par voie intraveineuse ou par voie digestive) se traduit par une augmentation rapide et considérable de la quantité d'insuline sécrétée par le pancréas. Cette action se prolonge pendant plusieurs heures.In vitro l'action directe du produit sur le pancréas a été démontrée sur le pancréas isolé et perfusé du rat, même à très faibles concentrations. — Chez la souris le RP 22410 administré chroniquementper os stimule la néogénèse des îlots de Langerhans et des cellules bêta. Il est donc doué de l'action bêtacytotrophe.
    Kurzfassung: Zusammenfassung Glisoxepid oder RP 22410 ist ein neuer, stark aktiver, blutzuckersenkender Sulfonylharnstoff. Je nachdem ob die Dosen in Gewichten oder Mol ausgedrückt werden, ist er am wachen Hund bei intravenöser Applikation 81 bzw. 131mal aktiver als Tolbutamid. Die blutzuckersenkende Wirkung zeigt sich nicht am vollständig pankreatektomierten Hund. -Diese Substanz stimuliert die Insulinsekretion.In vivo zeigt sich ihre Wirkung am anästhesierten oder wachen Hund in einer schnellen und beträchtlichen Erhöhung der vom Pankreas sezernierten Insulinmenge unabhängig davon ob sie intravenös oderper os verabreicht wird. Diese Wirkung bleibt über mehrere Stunden bestehen.In vitro wurde die direkte Wirkung der Substanz auf den isolierten und perfundierten Pankreas der Ratte auch in sehr geringen Konzentrationen nachgewiesen. -Bei der Maus stimuliert RP 22410 bei chronischer Verabreichungper os die Neubildung von Langerhansschen Inseln und B-Zellen. Sie besitzt daher eine betacytotrophe Wirkung.
    Notizen: Summary Glisoxepid or RP 22410 is a new very active hypoglycaemic sulphonylurea. In the normal conscious dog, RP 22410 administered intravenously was 81 or 131 times more active than tolbutamide, depending on whether the dose is expressed in grams or in moles. The hypoglycaemic effect did not occur in the totally pancreatectomized dog. — RP 22410 stimulated insulin secretion.In vivo in the anaesthetized or conscious dog, the action of the drug (whether it be administered intravenously or orally) resulted in a rapid and considerable increase of the amount of insulin secreted by the pancreas. This action lasted several hours.In vitro the direct action of the product on the pancreas was demonstrated on the isolated and perfused rat pancreas, even at very low concentrations. — In the mouse, prolonged oral administration of RP 22410 stimulated neogenesis of the islets of Langerhans and of the beta cells. It therefore possesses betacytotrophic action.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 24 (1983), S. 107-112 
    ISSN: 1432-0428
    Schlagwort(e): Insulin secretion ; adrenaline ; noradrenaline ; catecholamines ; dog ; blood glucose ; propranolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effects of adrenaline and noradrenaline infusions on pancreaticoduodenal venous insulin output were studied in anaesthetized normal dogs. Two experimental protocols were used. In the first, the dogs had a normal blood glucose level at the start of the catecholamine infusion (normoglycaemic dogs). In the second, the animals were made hyperglycaemic by a continuous glucose infusion (hyperglycaemic dogs). In the normoglycaemic dogs, adrenaline (0.5 μg · kg-1 · min-1) provoked hyperglycaemia accompanied by an increase in insulin output. Noradrenaline (0.5 μg · kg-1 · min-1) also caused an increase in insulin output but without any significant change in blood glucose. In hyperglycaemic dogs, adrenaline (2 μg · kg-1 · min-1) reduced the insulin response and enhanced the hyperglycaemia; noradrenaline (2 μg · kg-1 · min-1) markedly increased the insulin response (+ 2250%) without any significant change in blood glucose. Propranolol (0.3 mg/kg, IV) prevented the increase of insulin induced by noradrenaline. These findings show that, in the normal dog, adrenaline and noradrenaline infusions can produce opposite effects on insulin response depending on the experimental conditions.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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