Inhibitory effect of CuSO₄ on α-glucosidase activity in ddY mice.

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.