Epigenetic-mediated reprogramming of pancreatic endocrine cells

Type 1 diabetes (T1D) results from cell-mediated autoimmune destruction of insulin-secreting pancreatic beta cells (β-cells). In the context of T1D, the scarcity of organ donors has driven research to alternate sources of functionally competent, insulin-secreting β-cells as substitute for donor islets to meet the clinical need for transplantation therapy.

Experimental evidence of an inherent plasticity of pancreatic cells has fuelled interest in in vivo regeneration of β-cells. Transcriptional modulation and direct reprogramming of noninsulin secreting pancreatic α-cells to functionally mimic insulin-secreting β-cells is one of the promising avenues to the treatment of diabetes. Recent studies now show that adult progenitor and glucagon(+) α-cells can be converted into β-like cells in vivo, as a result of specific activation of the Pax4 gene in α-cells and curing diabetes in preclinical models.

The challenge now is to understand the precise developmental transitions mediated by endocrine transcription factors and co-regulatory determinants responsible for pancreatic function and repair.

Epigenetic-mediated regulation of transcription factor binding in pancreatic α-cells by specific drugs to direct reprogramming into functional insulin producing cells could be of potential innovative therapy for the treatment of T1D.