Interactions between PPAR Gamma and the Canonical Wnt/Beta-Catenin Pathway in Type 2 Diabetes and Colon Cancer

In both colon cancer and type 2 diabetes,metabolic changes induced by upregulation of the wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (ppar gamma) may help account for the frequent association of these two diseases. in both diseases,ppar gamma is downregulated while the canonical wnt/beta-catenin pathway is upregulated. in colon cancer,upregulation of the canonical wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex. as a result,a large part of cytosolic pyruvate is converted into lactate through activation of lactate dehydrogenase. lactate is extruded out of the cell by means of activation of monocarboxylate lactate transporter-1. this phenomenon is called warburg effect. ppar gamma agonists induce beta-catenin inhibition,while inhibition of the canonical wnt/beta-catenin pathway activates ppar gamma. © 2017 yves lecarpentier et al.