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.