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

Abstract EN

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.