Small Molecule-induced Beta-cell Regeneration from Alternate Cell Sources

Restoring functional pancreatic beta-cell mass in patients with type 1 diabetes would achieve insulin independence, and ultimately improve quality of life. Historically, animal models have represented the majority of work done to understand beta-cell regeneration. The outcomes of such studies have provided important insights on genetic approaches to replenish beta-cell mass, but these genetic perturbations limit the suitability of such methods for clinical purposes. An alternate discovery path involves the use of beta cells from stem-cell sources. Recent advances in the stem-cell field demonstrate the possibility of inducing pluripotent stem cells from somatic cells and subsequently differentiating them into beta cells, but these derived cells also face important barriers to their use. Pancreatic alpha cells represent an alternative cellular source, and mouse studies show that there is ample capacity for beta-cell reprogramming. For all of these cell sources, chemical compounds have several advantages over genetic approaches, in terms of their convenience of use and provision for temporal control, and represent a promising avenue to attain insulin independence. We present in this review the prospects of using small molecules to induce beta-cell regeneration from other cell types in the body.