ABSTRACT
Diethyldithiocarbamate sodium (DDC)--a compound forming complexes with metal ions-did not change the structure of endocrine pancreas and did not affect the glycemia after the repeated administration of a dose of 250 mg kg-1 while a single dose of 500 or 1000 mg kg-1 increased the glycemia for 2 to 4 h in most of rabbits tested. DDC injected in similar doses prevented a diabetogenic action of dithisone and of a number of 8-oxichinoline derivatives. This effect appeared very rapidly and persisted for several hours being dependent on a dose of DDC and on the interval between its administration and the injection of diabetogenic compounds. It was concluded that DDC forms stable complexes with zinc ions in pancreatic beta-cells which appear to be resistant towards the action of diabetogenic compounds directed selectively to the blocking of zinc ions too and thus to the development of experimental diabetes.
Subject(s)
Azo Compounds , Diabetes Mellitus, Experimental/prevention & control , Dithizone , Ditiocarb/therapeutic use , Hydroxyquinolines , Islets of Langerhans/drug effects , Oxyquinoline , Thiocarbamates/therapeutic use , Animals , Dithizone/antagonists & inhibitors , Ditiocarb/administration & dosage , Dose-Response Relationship, Drug , Female , Hyperglycemia/prevention & control , Islets of Langerhans/metabolism , Male , Oxyquinoline/antagonists & inhibitors , Rabbits , Zinc/antagonists & inhibitors , Zinc/metabolismABSTRACT
Experiments were conducted on rabbits. A study was made of the effect of administration of maninyl (glybenclamide) into the stomach in a dose of 10 mg/kg of body weight for 7 days on the blood glucose level, insulin and zinc content in the pancreatic islands, and on the "dithizone" diabetes development. Maninyl administration was accompanied by a significant glycemia reduction. The amount of deposited insulin and zinc determined histochemically was sharply reduced up to complete disappearance from the majority of beta-cells. "Dithizone" diabetes was not reproducible in animals given maninyl preliminarily: the required condition for induction of this affection was formation of zinc dithizonate in beta-cells.
Subject(s)
Azo Compounds/antagonists & inhibitors , Diabetes Mellitus, Experimental/prevention & control , Dithizone/antagonists & inhibitors , Glyburide/therapeutic use , Islets of Langerhans/drug effects , Animals , Blood Glucose/analysis , Glyburide/pharmacology , Histocytochemistry , Insulin/metabolism , Islets of Langerhans/metabolism , Rabbits , Zinc/metabolismABSTRACT
Administration of a nondiabetogenic complex-former-sodium diethyldithiocarbamate (SDEDTC) to rabbits prevented the appearance in beta-cells of the insular apparatus of histological and ultramicroscopic changes with the subsequent administration of a potent diabetogenic agent-ditisone. SDEDTC blocked the insular zinc and prevented ditisone from forming in the islets a complex with this metal producing a destructive action of beta-cells.
