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

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 and Farzad Esni ()
Additional contact information
Shakti Dahiya: University of Pittsburgh Medical Center
Mohamed Saleh: University of Pittsburgh Medical Center
Uylissa A. Rodriguez: University of Pittsburgh Medical Center
Dhivyaa Rajasundaram: University of Pittsburgh Medical Center
Jorge R. Arbujas: University of Pittsburgh Medical Center
Arian Hajihassani: University of Pittsburgh Medical Center
Kaiyuan Yang: Helmholtz Munich
Anuradha Sehrawat: University of Pittsburgh Medical Center
Ranjeet Kalsi: University of Pittsburgh Medical Center
Shiho Yoshida: University of Pittsburgh Medical Center
Krishna Prasadan: University of Pittsburgh Medical Center
Heiko Lickert: Helmholtz Munich
Jing Hu: University of Pittsburgh
Jon D. Piganelli: University of Pittsburgh Medical Center
George K. Gittes: University of Pittsburgh Medical Center
Farzad Esni: University of Pittsburgh Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-47972-4

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