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.
D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D003920:Diabetes Mellitus / Q000139:chemically induced; D005260:Female; D007328:Insulin / Q000096:biosynthesis* / Q000172:deficiency*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D011817:Rabbits; D014105:Tosyl Compounds; D015032:Zinc / Q000037:antagonists & inhibitors*; D000096926:Benzenesulfonamides
D000634:Aminoquinolines; D007328:Insulin; D014105:Tosyl Compounds; D015032:Zinc; C031480:8-(4-tolylsulfonylamino)quinoline; C031481:8-(methylsulfonylamino)quinoline; C031479:8-(4-benzenesulfonylamino)quinoline; D000096926:Benzenesulfonamides