Inhibition of α-glucosidase by vitamin D3 and the effect of vitamins B1 and B2

Abstract

α-Glucosidase is a vital enzyme in carbohydrate metabolism. Over-expression of this enzyme is correlated with hyperglycemia. The inhibitory effect of vitamin D₃ on α-glucosidase as well as its mechanism of action was investigated in this work. The results showed that vitamin D₃ exhibited stronger inhibition on α-glucosidase than acarbose with the IC₅₀ value of 1.28 × 10⁻⁴ mol L⁻¹, and the inhibition was a mixed-type mechanism through a multiphase kinetic process. The inhibition constant was determined to be (5.66 ± 0.03) × 10⁻⁵ mol L⁻¹. Vitamin D₃ interacted with α-glucosidase by hydrophobic interactions, and molecular docking further verified that the inhibitor inserted into the active site pocket of α-glucosidase and interacted with the amino residues, which induced the rearrangement and conformational changes of α-glucosidase, and might move to cover the active pocket, hindering the binding of the substrate leading to the inhibition of the enzyme activity. Moreover, it was found that vitamin D₃ combined with vitamin B₁ or vitamin B₂ exhibited significant synergistic effects on inhibition of α-glucosidase. This study has provided new insights into the role of vitamin D₃ in inhibiting α-glucosidase catalysis and offered useful information on the dietary recommendation of vitamin D₃ for the treatment of type 2 diabetes.