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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Acinar to β-like cell conversion through inhibition of focal adhesion kinase.
Nat. Commun. 15:3740 (2024)
Insufficient functional beta-cell mass causes diabetes; however, an effective cell replacement therapy for curing diabetes is currently not available. Reprogramming of acinar cells toward functional insulin-producing cells would offer an abundant and autologous source of insulin-producing cells. Our lineage tracing studies along with transcriptomic characterization demonstrate that treatment of adult mice with a small molecule that specifically inhibits kinase activity of focal adhesion kinase results in trans-differentiation of a subset of peri-islet acinar cells into insulin producing beta-like cells. The acinar-derived insulin-producing cells infiltrate the pre-existing endocrine islets, partially restore beta-cell mass, and significantly improve glucose homeostasis in diabetic mice. These findings provide evidence that inhibition of the kinase activity of focal adhesion kinase can convert acinar cells into insulin-producing cells and could offer a promising strategy for treating diabetes. A cure for diabetes could entail an effective cell replacement therapy through generation of new insulinproducing cells. In this study, we show that inhibition of focal adhesion kinase activity results in transdifferentiation of a subset of peri-islet acinar cells into functional insulin producing beta-like cells.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Pancreatic Exocrine Cells; Alpha-cells; Proliferation; Regeneration; Islets; Fak; Endocrine; Insulin; Dark; Mice
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 15,
Issue: 1,
Article Number: 3740
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Grants
Cochrane-Weber Endowed Funds for Diabetes Research
Research Advisory Committee (RAC) Children's Hospital of Pittsburgh of UPMC
JDRF
Children's Hospital
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
Research Advisory Committee (RAC) Children's Hospital of Pittsburgh of UPMC
JDRF
Children's Hospital
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)