Acinar to β-like cell conversion through inhibition of focal adhesion kinase.

Nature communications 2024 May 03

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Insufficient functional β-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 β-like cells. The acinar-derived insulin-producing cells infiltrate the pre-existing endocrine islets, partially restore β-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. © 2024. The Author(s).

Citation

Shakti Dahiya, Mohamed Saleh, Uylissa A Rodriguez, Dhivyaa Rajasundaram, Jorge R Arbujas, Arian Hajihassani, Kaiyuan Yang, Anuradha Sehrawat, Ranjeet Kalsi, Shiho Yoshida, Krishna Prasadan, Heiko Lickert, Jing Hu, Jon D Piganelli, George K Gittes, Farzad Esni. Acinar to β-like cell conversion through inhibition of focal adhesion kinase. Nature communications. 2024 May 03;15(1):3740