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Montane, JoelCorresponding AuthorDe Pablo, SaraAuthorCastano, CarlosAuthorRodriguez-Comas, JuliaAuthorObach, MerceAuthorVisa, MontseAuthorAlcarraz-Vizan, GemaAuthorNonell-Canals, AlfonsAuthorParrizas, MarcelinaAuthorServitja, Joan-MarcAuthorNovials, AnnaCorresponding Author

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December 19, 2017
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Amyloid-induced beta-cell dysfunction and islet inflammation are ameliorated by 4-phenylbutyrate (PBA) treatment

Publicated to: Faseb Journal. 31 (12): 5296-+ - 2017-12-01 31(12), DOI: 10.1096/fj.201700236R

Authors: Montane, Joel; de Pablo, Sara; Castano, Carlos; Rodriguez-Comas, Julia; Cadavez, Lisa; Obach, Merce; Visa, Montse; Alcarraz-Vizan, Gema; Sanchez-Martinez, Melchor; Nonell-Canals, Alfons; Parrizas, Marcelina; Servitja, Joan-Marc; Novials, Anna

Affiliations

Ctr Invest Biomed Red Diabet & Enfermed Metab Aso, Madrid, Spain      CIBER - Centro de Investigacion Biomedica en Red    CIBERDEM       - Author
Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Diabet & Obes Res Lab, Barcelona, Spain.      IDIBAPS    University of Barcelona    Hospital Clinic de Barcelona - Author
Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Diabet & Obes Res Lab, Barcelona, Spain      Hospital Clinic de Barcelona    University of Barcelona    IDIBAPS - Author
Mind Byte, Barcelona, Spain - Author
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Abstract

Human islet amyloid polypeptide (hIAPP) aggregation is associated with ?-cell dysfunction and death in type 2 diabetes (T2D). we aimed to determine whether in vivo treatment with chemical chaperone 4-phenylbutyrate (PBA) ameliorates hIAPP-induced ?-cell dysfunction and islet amyloid formation. Oral administration of PBA in hIAPP transgenic (hIAPP Tg) mice expressing hIAPP in pancreatic ? cells counteracted impaired glucose homeostasis and restored glucose-stimulated insulin secretion. Moreover, PBA treatment almost completely prevented the transcriptomic alterations observed in hIAPP Tg islets, including the induction of genes related to inflammation. PBA also increased ?-cell viability and improved insulin secretion in hIAPP Tg islets cultured under glucolipotoxic conditions. Strikingly, PBA not only prevented but even reversed islet amyloid deposition, pointing to a direct effect of PBA on hIAPP. This was supported by in silico calculations uncovering potential binding sites of PBA to monomeric, dimeric, and pentameric fibrillar structures, and by in vitro assays showing inhibition of hIAPP fibril formation by PBA. Collectively, these results uncover a novel beneficial effect of PBA on glucose homeostasis by restoring ?-cell function and preventing amyloid formation in mice expressing hIAPP in ? cells, highlighting the therapeutic potential of PBA for the treatment of T2D.-Montane, J., de Pablo, S., Castaño, C., Rodríguez-Comas, J., Cadavez, L., Obach, M., Visa, M., Alcarraz-Vizán, G., Sanchez-Martinez, M., Nonell-Canals, A., Parrizas, M., Servitja, J.-M., Novials, A. Amyloid-induced ?-cell dysfunction and islet inflammation are ameliorated by 4-phenylbutyrate (PBA) treatment.© FASEB.

Keywords

acidapoptosisdiabetesexpressionfibrilsiappinsulinmodelpancreatic isletspolypeptidestresstype-24-phenylbutyric acidAmyloidAnimalsDiabetesGlucose tolerance testHumansIappImmunohistochemistryInsulinInsulin-secreting cellsIslet amyloid polypeptideIslets of langerhansMaleMiceMice, transgenicMicroscopy, electron, transmissionPancreatic isletsPancreatic-isletsPhenylbutyratesReal-time polymerase chain reaction

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Faseb Journal due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2017, it was in position 8/85, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-16:

  • WoS: 25
  • Scopus: 26
  • Europe PMC: 20

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 43.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 43 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 4.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Montane Mogas, Joel) and Last Author (Montane Mogas, Joel).

the authors responsible for correspondence tasks have been Montane Mogas, Joel and Novials Sardà, Anna Maria.