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This work was supported by projects from the Instituto de Salud Carlos III (PI14/00447 and PI17/00879 to JMS and AN) co-funded by the Fondo Europeo de Desarrollo Regional (FEDER, European Union, A way to build Europe), by the Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), and by the CERCA Programme and grant 2014_SGR_520 (Generalitat de Catalunya). CIBERDEM is an initiative of the Instituto de Salud Carlos III. This work was developed at the Centre Esther Koplowitz (Barcelona).

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Moreno-Vedia, JAuthor
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4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity

Publicated to:Scientific Reports. 11 (1): 11878- - 2021-06-04 11(1), DOI: 10.1038/s41598-021-91311-2

Authors: de Pablo, Sara; Rodriguez-Comas, Julia; Diaz-Catalan, Daniela; Alcarraz-Vizan, Gema; Castano, Carlos; Moreno-Vedia, Juan; Montane, Joel; Parrizas, Marcelina; Servitja, Joan-Marc; Novials, Anna

Affiliations

Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona, Spain - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Pathogenesis & Prevent Diabet Grp, C Rossello 149-153, Barcelona 08036, Spain - Author

Abstract

Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of beta -cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). Treatment with chaperones has been associated with a decrease in endoplasmic reticulum stress leading to improved glucose metabolism. The aim of this work was to investigate whether the chemical chaperone 4-phenylbutyrate (PBA) prevents glucose metabolism abnormalities and amyloid deposition in obese agouti viable yellow (A(vy)) mice that overexpress hIAPP in beta cells (A(vy) hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when A(vy) hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese A(vy) hIAPP mice in fasting and fed conditions throughout the study. This effect was paralleled by a decrease in hyperinsulinemia. Importantly, PBA treatment reduced the prevalence and the severity of islet amyloid deposition in A(vy) hIAPP mice. Collectively, these results show that PBA treatment elicits a marked reduction of hyperglycemia and reduces amyloid deposits in obese and diabetic mice, highlighting the potential of chaperones for T2D treatment.

Keywords
accumulationbeta-cell dysfunctionglucoseiappinsulin-resistancemicepathogenesispolypeptidetoxicity4-phenylbutyric acidAccumulationAmyloidAnimalsBeta-cell dysfunctionDiabetes mellitus, experimentalDiabetes mellitus, type 2Disease models, animalEndoplasmic-reticulum stressFemaleGlucoseGlucose intoleranceGlucose tolerance testHomeostasisHyperglycemiaIappInsulin secretionInsulin-resistanceInsulin-secreting cellsIslet amyloid polypeptideIslets of langerhansMaleMiceMice, transgenicObesityPathogenesisPhenylbutyratesPolypeptideToxicity

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Scientific Reports due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary. 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 2025-05-06:

  • WoS: 4
  • Scopus: 4
  • Europe PMC: 2
  • OpenCitations: 2
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 2025-05-06:

  • 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: 30.
  • 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: 30 (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: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (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.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.11797/imarina9225665