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

Abstract Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). Treatment with chaperones has been associated with a decrease in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sara de Pablo, Júlia Rodríguez-Comas, Daniela Díaz-Catalán, Gema Alcarraz-Vizán, Carlos Castaño, Juan Moreno-Vedia, Joel Montane, Marcelina Parrizas, Joan-Marc Servitja, Anna Novials
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0369fa00d1f7444587242a36dc3bc794
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0369fa00d1f7444587242a36dc3bc794
record_format	dspace
spelling	oai:doaj.org-article:0369fa00d1f7444587242a36dc3bc7942021-12-02T15:56:57Z4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity10.1038/s41598-021-91311-22045-2322https://doaj.org/article/0369fa00d1f7444587242a36dc3bc7942021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91311-2https://doaj.org/toc/2045-2322Abstract Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-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 (Avy) mice that overexpress hIAPP in β cells (Avy hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when Avy hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese Avy 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 Avy 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.Sara de PabloJúlia Rodríguez-ComasDaniela Díaz-CatalánGema Alcarraz-VizánCarlos CastañoJuan Moreno-VediaJoel MontaneMarcelina ParrizasJoan-Marc ServitjaAnna NovialsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara de Pablo Júlia Rodríguez-Comas Daniela Díaz-Catalán Gema Alcarraz-Vizán Carlos Castaño Juan Moreno-Vedia Joel Montane Marcelina Parrizas Joan-Marc Servitja Anna Novials 4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
description	Abstract Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-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 (Avy) mice that overexpress hIAPP in β cells (Avy hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when Avy hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese Avy 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 Avy 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.
format	article
author	Sara de Pablo Júlia Rodríguez-Comas Daniela Díaz-Catalán Gema Alcarraz-Vizán Carlos Castaño Juan Moreno-Vedia Joel Montane Marcelina Parrizas Joan-Marc Servitja Anna Novials
author_facet	Sara de Pablo Júlia Rodríguez-Comas Daniela Díaz-Catalán Gema Alcarraz-Vizán Carlos Castaño Juan Moreno-Vedia Joel Montane Marcelina Parrizas Joan-Marc Servitja Anna Novials
author_sort	Sara de Pablo
title	4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
title_short	4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
title_full	4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
title_fullStr	4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
title_full_unstemmed	4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
title_sort	4-phenylbutyrate (pba) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0369fa00d1f7444587242a36dc3bc794
work_keys_str_mv	AT saradepablo 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT juliarodriguezcomas 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT danieladiazcatalan 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT gemaalcarrazvizan 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT carloscastano 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT juanmorenovedia 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT joelmontane 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT marcelinaparrizas 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT joanmarcservitja 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity AT annanovials 4phenylbutyratepbatreatmentreduceshyperglycemiaandisletamyloidinamousemodeloftype2diabetesandobesity
_version_	1718385369736544256

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

Ejemplares similares