Research ArticleRegenerative Medicine

GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β cell regeneration

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Science Translational Medicine  12 Feb 2020:
Vol. 12, Issue 530, eaaw9996
DOI: 10.1126/scitranslmed.aaw9996

Best buddies for β cells

Regeneration of insulin-producing pancreatic β cells is a key therapeutic strategy for diabetes. Previous efforts to stimulate β cell proliferation through combined inhibition of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) and TGFβ/SMAD signaling have had restricted clinical development due to their combined action on human cell types other than β cells. Ackeifi et al. show that glucagon-like peptide-1 receptor agonists partner with DYRK1A inhibitors to stimulate proliferation of functional β cells in cadaveric human pancreatic islets, with a relatively β cell–specific effect. Streptozocin-induced diabetic mice transplanted with human islets showed improved insulin secretion and glycemic control after in vivo combination treatment.

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