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Title: Targeting pancreatic islet PTP1B improves islet graft revascularization and transplant outcomes
Author: Figuereido, Hugo
Figueroa, Ana Lucia C.
García Alamán, Ainhoa
Fernandez Ruiz, Rebeca
Broca, Christophe
Wojtusciszyn, Anne
Gomis de Barbarà, Ramon
Malpique, Rita
Gasa, Rosa
Others: Universitat Oberta de Catalunya (UOC)
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Centre Hospitalier Universitaire de Montpellier
Keywords: pancreatic islet transplantation
Issue Date: 23-May-2019
Publisher: Science Translational Medicine
Citation: Figueiredo, H., Figueroa, A.L., Garcia, A., Fernandez-Ruiz, R., Broca, C., Wojtusciszyn, A., Malpique, R., Gasa, R. & Gomis, R. (2019). Targeting pancreatic islet PTP1B improves islet graft revascularization and transplant outcomes. Science Translational Medicine, 11(497), -. doi: 10.1126/scitranslmed.aar6294
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Abstract: Deficient vascularization is a major driver of early islet graft loss and one of the primary reasons for the failure of islet transplantation as a viable treatment for type 1 diabetes. This study identifies the protein tyrosine phosphatase 1B (PTP1B) as a potential modulator of islet graft revascularization. We demonstrate that grafts of pancreatic islets lacking PTP1B exhibit increased revascularization, which is accompanied by improved graft survival and function, and recovery of normoglycemia and glucose tolerance in diabetic mice transplanted with PTP1B-deficient islets. Mechanistically, we show that the absence of PTP1B leads to activation of hypoxia-inducible factor 1a -independent peroxisome proliferator-activated receptor y coactivator 1a/estrogen-related receptor a signaling and enhanced expression and production of vascular endothelial growth factor A (VEGF-A) by B cells. These observations were reproduced in human islets. Together, these findings reveal that PTP1B regulates islet VEGF-A production and suggest that this phosphatase could be targeted to improve islet transplantation outcomes.
Language: English
ISSN: 1946-6234MIAR
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