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The IGFBP3/TMEM219 pathway regulates beta cell homeostasis

التفاصيل البيبلوغرافية
العنوان: The IGFBP3/TMEM219 pathway regulates beta cell homeostasis
المؤلفون: D'Addio F., Maestroni A., Assi E., Ben Nasr M., Amabile G., Usuelli V., Loretelli C., Bertuzzi F., Antonioli B., Cardarelli F., El Essawy B., Solini A., Gerling I. C., Bianchi C., Becchi G., Mazzucchelli S., Corradi D., Fadini G. P., Foschi D., Markmann J. F., Orsi E., Skrha J., Camboni M. G., Abdi R., James Shapiro A. M., Folli F., Ludvigsson J., Del Prato S., Zuccotti G., Fiorina P.
المساهمون: D'Addio, F., Maestroni, A., Assi, E., Ben Nasr, M., Amabile, G., Usuelli, V., Loretelli, C., Bertuzzi, F., Antonioli, B., Cardarelli, F., El Essawy, B., Solini, A., Gerling, I. C., Bianchi, C., Becchi, G., Mazzucchelli, S., Corradi, D., Fadini, G. P., Foschi, D., Markmann, J. F., Orsi, E., Skrha, J., Camboni, M. G., Abdi, R., James Shapiro, A. M., Folli, F., Ludvigsson, J., Del Prato, S., Zuccotti, G., Fiorina, P.
سنة النشر: 2022
المجموعة: ARPI - Archivio della Ricerca dell'Università di Pisa
مصطلحات موضوعية: Adult, Animal, Cells, Cultured, Diabetes Mellitus, Type 1, Type 2, Female, Homeostasi, Human, Immunoblotting, Insulin-Like Growth Factor Binding Protein 3, Insulin-Secreting Cell, Male, Membrane Protein, Mice, Inbred C57BL, Inbred NOD, Knockout, Transgenic, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Gene Expression Regulation
الوصف: Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients’ cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
نوع الوثيقة: article in journal/newspaper
وصف الملف: ELETTRONICO
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35115561; info:eu-repo/semantics/altIdentifier/wos/WOS:000752207900013; volume:13; issue:1; firstpage:684; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/11568/1136917Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85124057555
DOI: 10.1038/s41467-022-28360-2
الإتاحة: https://doi.org/10.1038/s41467-022-28360-2Test
http://hdl.handle.net/11568/1136917Test
رقم الانضمام: edsbas.1E6F5F4C
قاعدة البيانات: BASE
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