Although the mechanisms which underlie the increased expression of MAD2B under hyperglycaemia are still unknown, the present study for the first time demonstrates that MAD2B contributes to neurons undergoing apoptosis via APC-cyclin B1 pathway, suggesting a new pathogenic pathway governing cellular responses to hyperglycaemia, which may provide an important therapeutic strategy to prevent neuron injury in diabetic encephalopathy. Here, MAD2L2 is linked to diabetic encephalopathy.