Effect of flavonoids on basal and insulin-stimulated 2-deoxyglucose uptake in adipocytes

Scope: The adipose tissue is a major site of insulin action and contributes substantially to energy homeostasis. Insulin increases the extraction of glucose from circulation into adipose tissue by recruiting the glucose transporter GLUT4 to the plasma membrane. It has been proposed that dietary flavonoids may interfere with glucose transport processes. Methods and results: We have used murine 3T3-L1 adipocytes and isolated mature human adipocytes to assess the interaction of selected flavonoids with glucose uptake, both in the basal state and after insulin stimulation. Kinetic characterization of 2-deoxyglucose uptake in the basal state revealed in both cell types an apparent Km of around 8mM with no change in affinity but a significant increase in maximal influx in the presence of insulin. A screening of representative flavonoids of different structural classes revealed the flavanone naringenin and the isoflavone daidzein to affect glucose transport significantly with half-maximal inhibition at concentrations of around 60-80 mM for basal and 70-110 mM for insulin-stimulated glucose uptake in both 3T3-L1 adipocytes and mature human adipocytes. Conclusion: Considering attainable plasma concentrations of flavonoids in vivo, we assume that even under physiological conditions naringenin and daidzein could impair glucose removal from plasma, which may pose a risk to patients with diabetes mellitus.