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-cateninsignaling 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 canonicalWnt/ beta-cateninpathway is upregulated. In colon cancer, upregulation of the canonicalWnt system induces activation of pyruvate dehydrogenase kinaseand deactivation of the pyruvate dehydrogenase complex. As a result, a large part of cytosolic pyruvate is converted into lactatethrough activation of lactate dehydrogenase. Lactateis extruded out of the cell by means of activation of monocarboxylate lactatetransporter-1. This phenomenon is called Warburg effect. PPAR gamma agonists induce beta-catenininhibition, while inhibition of the canonicalWnt/ beta-cateninpathway activates PPAR gamma.