We have published recently that type 2 diabetes can induce cell centrosome amplification, due to the action of high glucose, palmitic acid and insulin, and ROCK1 and 14-3-3σ are signal mediators. In this study, we further investigated the molecular mechanisms of the centrosome amplification in colon cancer HCT116 cells. Treatment of the cells with high glucose, palmitic acid and insulin increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) as well as the spindle- and kinetochore-associated protein 1 (SKA1), knockdown of each of which resulted in the inhibition of the treatment-triggered centrosome amplification. Knockdown of PPARγ inhibited the treatment-evoked increase in SKA1 level, while knockdown of SKA1 did not modify the treatment- increased PPARγ level. We found a predicted binding site for PPARγ in the promoter region of the SKA1 gene from the JASPAR database. Experimental results showed that the treatment increased the mRNA level of SKA1, which could be inhibited by PPARγ chemical inhibitor or siRNA. Moreover, we were able to show that PPARγ could bind to the binding site in the SKA1 gene promoter, which was increased by the experimental treatment. In conclusion, it is suggest that the pathophysiological factors in type 2 diabetes, high glucose, palmitic acid and insulin, induce the cell centrosome amplification through PPARγ-SKA1 pathway in which PPARγ increases the expression of SKA1 via directly enhancing the SKA1 gene transcription.