Author, as appears in the article.: 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;

Department: Medicina i Cirurgia

URV's Author/s: Moreno Vedia, Juan

Keywords: Toxicity Polypeptide Pathogenesis Mice Insulin-resistance Iapp Glucose Endoplasmic-reticulum stress Beta-cell dysfunction Accumulation toxicity polypeptide pathogenesis mice insulin-resistance iapp glucose beta-cell dysfunction accumulation

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.

Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Letras / linguística Interdisciplinar Geografía Geociências Farmacia Engenharias iv Engenharias iii Engenharias ii Enfermagem Educação física Educação Economia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Biotecnología Biodiversidade Astronomia / física

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: juan.moreno@urv.cat juan.moreno@urv.cat

Author identifier: 0000-0002-2673-3822 0000-0002-2673-3822

Record's date: 2022-01-30

Papper version: info:eu-repo/semantics/publishedVersion

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Scientific Reports. 11 (1):

APA: de Pablo, Sara; Rodriguez-Comas, Julia; Diaz-Catalan, Daniela; Alcarraz-Vizan, Gema; Castano, Carlos; Moreno-Vedia, Juan; Montane, Joel; Parrizas, Mar (2021). 4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity. Scientific Reports, 11(1), -. DOI: 10.1038/s41598-021-91311-2

Article's DOI: 10.1038/s41598-021-91311-2

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications