Summary
A new hypogylcaemic sulphonylurea HB 419 (Glybenzcyclamide) was injected intravenously into normal dogs (0.25 mg/kg). The drug produced within 30 min a fall in the concentration of plasma glucose and a rise in the concentration of immunoreactive insulin (IRI). When the alpha-adrenergic blocking agent phentolamine (5 mg per dog) was injected prior to the administration of HB 419, the rise in the concentration of plasma IRI was markedly potentiated. Insulin secretion was not appreciably stimulated by HB 419 when animals were treated with the beta-adrenergic blocking agent Kö 592, 1-(3-methylphenoxy)-3-isopropylaminopropanol-2-hydrochloride (0.1 mg/kg). The results of these experiments suggest that the mechanism of action of HB 419 on the pancreatic islets involves beta-adrenergic stimulation.
Résumé
Un nouveau sulfonylurée hypoglycémiant, le HB 419 (glybenzcyclamide) a été injecté par voie intraveineuse des chiens normaux (0.25 mg/kg). Dans les 30 min, la drogue provoquait une chute de la concentration de glucose plasmatique et une augmentation de la concentration d'insuline immunoréactive (IRI). Lorsque l'on injectait de la phentolamine (5 mg par chien), agent bloquant alpha-adrénergique, avant l'administration de HB 419, l'élévation de la concentration d'IRI plasmatique était potentialisée de façon prononcée. La sécrétion d'insuline n'était pas stimulée de façon appréciable par le HB 419 quand les animaux étaient traités avec un agent bloquant bêta-adrénergique, le Kö 592, chlorhydrate de 1-(3-méthylphenoxy)-3-isopropylaminopropanol-2 (0.1 mg/kg). Les résultats de ces expériences suggèrent que le mécanisme d'action du HB 419 sur les îlots pancréatiques implique la stimulation bêta-adrénergique.
Zusammenfassung
Normale Hunde erhielten 0.25 mg/kg des neuen blutzuckersenkenden Sulfonylharnstoffs HB 419 (Glybenzcyclamid) intravenös. Das Mittel rief innerhalb einer halben Stunde einen Abfall des Blutzuckers und einen Anstieg der Serumspiegel des immunoreaktiven Insulins (IRI) hervor. Die Erhöhung der Seruminsulinspiegel ließ sich wesentlich verstärken, wenn vor der HB 419-Gabe der alpha-Rezeptorenblocker Phentolan (5 mg/Hund) verabreicht wurde. Die Zufuhr des β-Rezeptorenblockers Kö 592, 1-(3-methylphenoxy)-3-isopropylaminopropanol-2-hydrochlorid (0.1 mg/kg) hob den HB 419-Effekt auf die Insulinsekretion weitgehend auf. Die Untersuchungsergebnisse deuten darauf hin, daß die Wirkung von HB 419 auf die Pankreasinseln über eine β-adrenerge Stimulation erfolgt.
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Sirek, O.V., Vigas, M., Niki, A. et al. Beta-adrenergic stimulation and insulin release in dogs following HB 419. Diabetologia 5, 207–210 (1969). https://doi.org/10.1007/BF01212085
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DOI: https://doi.org/10.1007/BF01212085