TY - JOUR
T1 - Protein disulfide isomerase ameliorates β-cell dysfunction in pancreatic islets overexpressing human islet amyloid polypeptide
AU - Montane, Joel
AU - de Pablo, Sara
AU - Obach, Mercè
AU - Cadavez, Lisa
AU - Castaño, Carlos
AU - Alcarraz-Vizán, Gema
AU - Visa, Montserrat
AU - Rodríguez-Comas, Júlia
AU - Parrizas, Marcelina
AU - Servitja, Joan Marc
AU - Novials, Anna
N1 - Funding Information:
This work was supported by grants PI11/00679 and PI14/00447 , within the framework of the Plan Estatal I + D + I 2013–2016 and co-financed by the ISCIII-Subdirección General de Evaluación y Fomento de la investigación el Fondo Europeo de Desarrollo Regional (FEDER; Una manera de hacer Europa), by Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and with the support of project number 2014_SGR_520 of the Department of Economy and Knowledge of the Government of Catalonia.
Funding Information:
JM is a recipient of an IDIBAPS Postdoctoral Fellowship-BIOTRACK, supported by the European Community's Seventh Framework Programme (ECFP7/2007–2013) under grant agreement number 229673 . LC is a recipient of Fundação da Ciência e Tecnologia (FCT-PhD) fellowship SFRH/BD/65645/2009 financed by POPH-QREN .
Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - 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.
AB - 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.
KW - Amyloid
KW - Chaperones
KW - Diabetes
KW - IAPP
UR - https://www.scopus.com/pages/publications/84949032785
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000368949700006&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.mce.2015.11.018
DO - 10.1016/j.mce.2015.11.018
M3 - Article
C2 - 26607804
AN - SCOPUS:84949032785
SN - 0303-7207
VL - 420
SP - 57
EP - 65
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -
SDG 3 Good Health and Well-being