Reprogramming Cells to Make Insulin

Abstract

Type 1 diabetes is a disease characterized by the destruction of insulin-secreting β-cells in the pancreas. Individuals are treated for this disease with lifelong insulin replacement. However, one attractive treatment possibility is to reprogram an individual's endogenous cells to acquire the ability to secrete insulin, essentially replacing destroyed β-cells. Herein, we review the literature on the topic of reprogramming endodermal cells to produce insulin.

Keywords: cell plasticity; enteroendocrine cell; gut endocrine system; pancreatic β-cell; stem cell differentiation.

Figure 1.

Schematic depicting tissues that can be reprogrammed to produce insulin. It is possible to transdifferentiate cells derived from intestine, stomach, liver, pancreas, and gallbladder into cells that make insulin. In the intestine and stomach, this is accomplished by overexpression of Pdx1, MafA, and Ngn3 (PMN) or ablation of Foxo1. Cells from liver, pancreas, and gallbladder are also transdifferentiated by PMN. Furthermore, Pax4 overexpression or Arx loss triggers this conversion in pancreatic cells, whereas the increase of Pax6 aids in the transdifferentiation of gallbladder cells. Gain-of-function factors are depicted in purple, whereas those requiring loss-of-function are shown in blue.