Therapeutic potential of pancreatic PAX4-regulated pathways in treating diabetes mellitus

Abstract

The high prevalence of diabetes mellitus (DM) in our society, together with the fact that current treatments are only palliative and do not prevent the development of life threatening side effects, highlights the urgent need for novel therapies targeting the root cause of the disease. Independent of the etiology of DM, the definitive therapeutic approach will imply the restitution of an adequate functional b-cell mass capable of compensating for the insulin demand of the organism. The recent demonstration of heterogeneity within the islets as well as their innate plasticity has encouraged the development of studies aiming at potentiation of the regenerative capacity of islets. In this regard, factors implicated in pancreas ontogeny as well as in the adaptation processes that take place in the islets under situations of increased insulin demand have gained much interest. One of these factors is the transcription factor PAX4, required for b-cell formation during embryonic development and implicated in adult b-cell adaptation under stress situations. Here we review the therapeutic potential of PAX4 as well as its downstream targets for the development of novel treatments for DM.