title: Inhibitory effect of CuSO₄ on α-glucosidase activity in ddY mice.
abstract: We investigated the effects of divalent alkaline earth and first-row transition metal and zinc ions on α-glucosidase activity in vitro and in vivo. CuSO₄ and ZnSO₄ exhibited a high α-glucosidase inhibitory effect in vitro. The IC(50) values of CuSO₄ were 0.77 ± 0.01 (substrate; maltose) and 0.78 ± 0.01 (substrate; sucrose), and those of ZnSO₄ were 5.49 ± 0.14 (substrate; maltose) and 4.70 ± 0.06 (substrate; sucrose) for yeast α-glucosidase. On the basis of Lineweaver-Burk plots, both CuSO₄ and ZnSO₄ exhibited different modes of inhibition against α-glucosidase. Subsequently, oral glucose and sucrose tolerance tests (OGTT and OSTT) were performed on non-diabetic ddY mice to examine the effect of the metal ions on their blood glucose levels. As a result of single oral administration of CuSO₄ in non-diabetic ddY mice, a significant and potent lowering of the blood glycemic response toward disaccharide, sucrose, ingestion was observed at 45 min after doses of 0.08 and 0.24 mmol kg(-1) body weight. In contrast, the CuSO₄ administration showed no suppression of the elevation of blood glucose levels in mice after a monosaccharide, glucose, administration. These results indicate that CuSO₄ suppresses disaccharide digestion by inhibiting α-glucosidase activity in the epithelium of the small intestine, suggesting that antidiabetic Cu complexes with some ligands have a similar action mechanism to that of α-glucosidase inhibitor, acarbose, currently used for clinical purposes.
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto, Japan. yutaka@mb.kyoto-phu.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Ryoko
authors.initials: R
authors.lastname: Hirata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hattori
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002240:Carbohydrate Sequence; D019327:Copper Sulfate / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors; D020128:Inhibitory Concentration 50; D007421:Intestine, Small / Q000201:enzymology; D007700:Kinetics; D016014:Linear Models; D008320:Maltose / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D012440:Saccharomyces / Q000201:enzymology; D013395:Sucrose / Q000378:metabolism; D028561:Transition Elements / Q000494:pharmacology; D019287:Zinc Sulfate / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005656:Fungal Proteins; D065089:Glycoside Hydrolase Inhibitors; D028561:Transition Elements; D013395:Sucrose; D008320:Maltose; D019287:Zinc Sulfate; D000520:alpha-Glucosidases; D019327:Copper Sulfate; D020909:Acarbose