Abstract

Diabetogenic Zinc Binding B-Cytotoxic Chemicals: Mechanisms of Action and Methods for Prevention of Diabetes

Mechanisms of diabetogenic action of diabetogenic zincbinding chemicals (DZBC) as Dithizon and derivatives of 8-oxyquinolin and methods of prevention of diabetes caused by their were investigated. It was established that: a) injection of diabetogenic doses of DZBC as 30-50 mg/kg result forming in bytoplasm of B-cells of chelat complexes Zn-DZBC within a few minutes; b) by electron microscopy it was showed that presence of complex in B-cells within 15-20 min result destruction and death of majority B-cells and developing of 1 type diabetes in animals; c) destruction of B-cells started by destroying of B-granules concentrated deposited form of insulin as Zn-insulin; d) prevention of formation of comlex in B-cells by 2 ways (complete elimination of Zn-ions from B-cells by Glibenclamide or binding of Zn-ions by not diabetogenic chelators as Na salt of Diethyl-dithiocarbamic acid, by Cystein and recovered form of Glutathion completely protect B-cells of formation of complex and of developing of diabetes in 85-95% of animals for period of binding of Zn-ions (12-24 h); e) Xanthurenic Acid formed in animals and human as result of disturbances of tryptophan metabolism possess same mechanism of action as other DZBC but diabetes developed more slowly because XA is synthesised in organism more slowly that is why not possible to destroy majority of B-cells as in result of injection of diabetogenic doses of other DZBC; f) they are only one real way for prevention action of XA- partial or mo complete inhibition of endogene synthesis of XA by administration of Pyridoxine (P) within long time due to ability of P to restore amount of Pyridoxal-5-Phosphate which protect endogene synthesis of XA; two other ways (elimination of Zn-ions and not diabetogenic binding of its) not possible to use for protect developing of diabetes or to reduce its symptoms.


Author(s):

Gabit G Meyramov, Aizhan G Abdraimova Meyramova



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