Cytoplasmic vacuolation of pancreatic beta cells of rats after oral administration of a derivative of isoquinoline.
beta cells in islets of Langerhans were studied in Sprague-Dawley rats dosed by gavage with 0 (control), 75, 150, 250 or 300 mg/kg body wt/day S-H 966 BS [1-(1-oxido-4-thiomorpholino)-3-(1-piperazinyl)], an isoquinoline derivative. All doses caused a significant and dose-dependent increase in serum glucose (diabetes mellitus). At 250 mg/kg, degranulation of beta cells was discovered after 1 day and vacuole formation after 2 days. Ultrastructural alterations compared well with that seen after treatment with cyproheptadine and other structurally related compounds. The vacuolation of beta cells was fully developed following 6 weeks of daily treatment, when a dose-dependent elevation of blood glucose was first observed. The effects were more severe in males than in females. Lesions were reversible within 6 weeks except at 300 mg/kg in males.
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D003533:Cyproheptadine / Q000633:toxicity; D003593:Cytoplasm / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000648:ultrastructure; D007546:Isoquinolines / Q000633:toxicity*; D008297:Male; D009940:Organoids / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014617:Vacuoles / Q000187:drug effects*
D005343:Fibrinolytic Agents; D007546:Isoquinolines; D003533:Cyproheptadine; C050077:SH 966 BS; D000469:Alkaline Phosphatase; C039109:isoquinoline