Considering our results that GSK3B and Snail controlled the transcription of CUL1, we tested if the genetic manipulations of GSK3B and Snail could regulate T2D- and DSN-like defects in Drosophila. Sensory neuron-specific expression of GSK3BDN or Snail induced the axonal degeneration and death of leg sensory neurons (Fig. 6g and Supplementary Fig. 8k, l) and reduced the jumping responses to heat stimuli (Fig. 6h, i) in fruit flies. Here, CUL1 is linked to type 2 diabetes mellitus.