We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to (...) promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.Also watch the Video Abstract. (shrink)