title: Protein disulfide isomerase ameliorates β-cell dysfunction in pancreatic islets overexpressing human islet amyloid polypeptide.
abstract: Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits in islets of type 2 diabetic patients. hIAPP misfolding and aggregation is one of the factors that may lead to β-cell dysfunction and death. Endogenous chaperones are described to be important for the folding and functioning of proteins. Here, we examine the effect of the endoplasmic reticulum chaperone protein disulfide isomerase (PDI) on β-cell dysfunction. Among other chaperones, PDI was found to interact with hIAPP in human islet lysates. Furthermore, intrinsically recovered PDI levels were able to restore the effect of high glucose- and palmitate-induced β-cell dysfunction by increasing 3.9-fold the glucose-stimulated insulin secretion levels and restoring insulin content up to basal control values. Additionally, PDI transduction decreased induced apoptosis by glucolipotoxic conditions. This approach could reveal a new therapeutic target and aid in the development of strategies to improve β-cell dysfunction in type 2 diabetic patients.
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Joel
authors.initials: J
authors.lastname: Montane
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: de Pablo
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Obach
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cadavez
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Castaño
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Alcarraz-Vizán
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Visa
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Júlia
authors.initials: J
authors.lastname: Rodríguez-Comas
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Marcelina
authors.initials: M
authors.lastname: Parrizas
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Joan Marc
authors.initials: JM
authors.lastname: Servitja
authors.affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain. Electronic address: anovials@clinic.ub.es.
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D014020:Tissue Extracts / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D018832:Molecular Chaperones; D014020:Tissue Extracts; D019308:Palmitic Acid; D019704:Protein Disulfide-Isomerases; D005947:Glucose
keywords: Amyloid; Chaperones; Diabetes; IAPP