Advances in drug discovery for human beta cell regeneration
The numbers of insulin-secreting pancreatic beta cells are reduced in people with type 1 and type 2 diabetes. Driving beta cell regeneration in the pancreases of people with diabetes would be an attractive approach to reversing diabetes. While adult human beta cells have long been believed to be terminally differentiated and, therefore, irreversibly quiescent, it has become clear over recent years that this is not true. More specifically, both candidate and unbiased high-throughput screen approaches have revealed several classes of molecules that are clearly able to induce human beta cell proliferation. Here, we review recent approaches and accomplishments in human beta cell regenerative drug discovery. We also list the challenges that this rapidly moving field must confront to translate beta cell regenerative therapy from the laboratory to the clinic.
KeywordsBeta cell Diabetes Drug discovery High-throughput screen Human Pancreas Proliferation Regeneration Review
Cell-division cycle-like kinases
Dual-specificity tyrosine phosphorylation-regulated kinase
Glycogen synthase kinase
Nuclear factor activated in T cells
We thank A. Garcia-Ocaña, D. Scott, M. Donovan, R. DeVita, R. Sanchez, C. Argmann and E. Schadt, all at the Icahn School of Medicine at Mount Sinai (New York, NY, USA), for invaluable discussions while the work described herein unfolded. We also apologise in advance to authors whose work we were unable to cite or discuss because of space limitations.
All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.
This work was supported by the Foundation for Diabetes Research (FDR), the Human Islet and Adenoviral Core (HIAC) of the Einstein-Sinai Diabetes Research Centre (E-S DRC), the Human Islet Research Network (HIRN) and by NIH/NIDDK grants (P-30 020541, UC-4 104211, R-01 105015, R-01 55023) and a JDRF grant (2-SRA-2015-62).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
- 55.Ogawa Y, Nonaka Y, Goto T et al (2010) Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat Commun 1:86Google Scholar