Inhibitory effect of CuSO4 on alpha-glucosidase activity in ddY mice

We investigated the effects of divalent alkaline earth and first-row transition metal and zinc ions on alpha-glucosidase activity in vitro and in vivo. CuSO4 and ZnSO4 exhibited a high alpha-glucosidase inhibitory effect in vitro. The IC50 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 alpha-glucosidase. On the basis of Lineweaver-Burk plots, both CuSO4 and ZnSO4 exhibited different modes of inhibition against alpha-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 alpha-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 alpha-glucosidase inhibitor, acarbose, currently used for clinical purposes.