Studies on diabetes mellitus after ventromedial hypothalamic lesions in adult and aged rats.

The signs of obesity and diabetes in 49 adult and 56 aged female Wistar rats were studied following complete and histologically confirms bilateral lesions of ventromedial hypothalamic nuclei. Persistent diabetes was found in 14 out of a total of 56 aged animals, while in a group of 49 adult females only one animal showed definite signs of this disease. In addition, several changes of lipid and glucose metabolism together with increased level of immunoreactive insulin and severe changes in the histological picture of pancreatic islets and beta-cells were observed.

Dithisone diabetes in rabbits and its prevention by sulfhydryl and imidazole containing compounds.

Diabetogenic action of dithisone was investigated in a total of 368 adult rabbits and 53 young animals between 10 h and 31 days of age. The diabetes was found in 95% of animals injected with dithisone and various forms of this disease were observed: 1. long-term diabetes without any signs of normalization of glycemia; 2. diabetes with periodical remissions; 3. several cases with a definite remission. The diabetes did not appear in young animals during certain periods of life in which the concentration of zinc in pancreatic islets was very low. It was possible to prevent the development of this disease by the administration of some compounds containing sulfhydryl or imidazole groups (cysteine, SH-glutathione, dimercaptopropanol (BAL), unithiol (sodium 2,3-dimercaptopropansulfonate), (histidine) and the diabetes also did not appear in such animals in which a majority of zinc was removed by glybenclamide. From these observations it was concluded that the development of diabetes after dithisone depends on the formation of dithisone complex with zinc in beta-cells.

Primary insulin insufficiency after blocking of zinc in pancreatic beta-cells.

Diabetogenic effects of various analogues of 8-aminoquinoline were studied. Out of 10 compounds investigated only three showed diabetogenic properties: 8-(p-tolylsulfonylamino)-quinoline, 8-(p-benzenesulfonylamino)-quinoline and 8-(p-methylsulfonylamino)-quinoline. After the injection of these compounds a long term persistent hyperglycemia took place in rabbits and also degenerative changes of insulin producing cells in pancreatic islets were found. All above compounds form stable complexes with zinc in beta-cells and their diabetogenic action diminished together with their ability to form such complexes. Thus, it may be assumed that a formation of these complexes may be one of possible mechanisms of primary insulin insufficiency.

Preventive effect of diethyldithiocarbamate on experimental diabetes produced by dithisone and 8-oxychinoline.

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.