Aim: 

To evaluate the effects of soy-derived isoflavones genistein and daidzein in physiological concentrations over insulin resistance (IR) in the adipocyte cell line 3T3-L1 and in skeletal muscle cell line L6.

Methods: 

After cell differentiation, we induced IR with TNF (20 ng/mL) –for 3T3-L1- or C2 ceramide (25-100 mM) –for L6 myotubes-. Thereafter, insulin was added with isoflavones at doses achieved under dietary soy supply in humans (0.1-5mM). Insulin signaling was checked using western-blot and insulin action was evaluated through fatty acid incorporation and high resolution respirometry.

Results: 

Isoflavone addittion led to a dose-dependent recovery response over IR inhibitory effects in AKT Ser 473 phosphorylation. This molecular effect was also linked to reversal of inhibition over fatty acid intake in 3T3-L1 due to IR. Those isoflavones did not act on insulin receptor itself or IRS phosphorylation. The isoflavone-linked mechanisms involved estrogen receptor-dependent pathways and it also included changes in mitochondrial respiratory function.

Conclussions: 

Genistein and daidzein at physiological doses prevent, using fast-acting mechanisms, inhibition of insulin signaling in 3T3-L1 and L6 cell lines, suggesting acute responses insulin potentiating after isoflavone-containing meals.