Transcription factors as therapeutic targets for diabetes

Abstract

Background: Islet cell implantation and pancreas transplantation have been used as treatments for diabetes but are limited by the shortage of donors and the requirement for lifelong immunosuppression. As an alternative, the generation of surrogate insulin-producing cells has been an area of interest for many researchers. Understanding how pancreatic β-cells are generated during pancreas development will provide information that can be applied to generating surrogate β-cells. Objective: To outline the current knowledge of pancreas development and differentiation, with a focus on the regulatory network of pancreas-enriched transcription factors and their targets. Methods: A review of relevant literature. Conclusions: Pancreatic and duodenal homeobox 1 (Pdx1), Neurogenin 3 (Ngn3), and musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) have been shown to play essential roles in pancreas development and β-cell differentiation, and gain-of-function approaches indicate the potency of these factors for inducing differentiation of non-β-cells into insulin-producing cells, which could lead to a novel therapy to cure diabetes.

Keywords::

• diabetes
• MafA
• Ngn3
• Pdx1

Acknowledgments

We thank Helena Akiko Popiel (Osaka University Graduate School of Medicine) for valuable comments on the manuscript.