Using a high throughput-compatible assay to screen for potential α-glucosidase inhibitors, we found that the β-lactam antibiotic ceftezole exhibited potent α-glucosidase inhibitory activity. In in vitro α-glucosidase assays, ceftezole was shown to be a reversible, non-competitive inhibitor of yeast α-glucosidase with a Ki value of 5.78x10−7 M when the enzyme mixture was pretreated with ceftezole. Using an in vivo streptozotocin-induced mouse model, we confirmed that blood glucose levels decreased by 30% 20 min after ceftezole treatment (10 mg/kg/day). Expression levels of glycogen synthase kinase-3, peroxisome proliferator-activated receptor-γ, and uncoupling protein-3 mRNA were also slightly decreased compared to controls following ceftezole treatment. Taken together, these in vivo and in vitro results suggest that ceftezole may be a clinically useful anti-diabetic compound.

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