Hypoglycemic effect of copper(II) acetate imidazole complexes

The effect of copper(II) complexes on glucose metabolism was studied in normal and streptozotocin-induced diabetic rats. The copper(II) complexes used were bis(acetato)tetrakis(imidazole) copper (II), [Cu(OAc)2(Im)4], bis(acetato)bis(2-methylimidazole) copper(II), [Cu(OAc)2(2mIm)2], bis(acetato)bis(1,2-dimethylimidazole) copper(II), [Cu(OAc)2(1,2dmIm)2], and bis(acetato)bis(mu-acetato)tetrakis(N-methylimidazole) copper(II) hexaaquo, [Cu2(OAc)4-(NmIm)4].6H2O. Intramuscular administration of various doses of Cu(OAc)2(Im)4 ranging from 10 to 100 mg/kg body mass to overnight fasted rats decreased blood glucose levels in a dose-dependent manner. Maximum hypoglycemic effect was observed 3 h after administration and lasted for at least 6 h. Treatment with 100 mg/kg body mass of Cu(OAc)2(Im)4 caused hypoglycemic shock, which was irreversible and even lethal. Blood insulin levels were reduced sharply during this hypoglycemic shock. Similar changes in blood glucose level were achieved using Cu(OAc)2(2mIm)2. The same pattern of hypoglycemia, although less pronounced, was observed for Cu2(OAc)4(NmIm)4.6H2O and Cu(OAc)2(1,2dmIm)2. Binary copper(II) acetate complex, the ligand imidazole, and the inorganic form of copper, such as copper(II) chloride, had no significant effect on blood glucose level. These results indicate that the hypoglycemic activity of these complexes varies with the imidazole ligand and structure of the complex.