Protein disulfide isomerase ameliorates β-cell dysfunction in pancreatic islets overexpressing human islet amyloid polypeptide

Joel Montane, Sara de Pablo, Mercè Obach, Lisa Cadavez, Carlos Castaño, Gema Alcarraz-Vizán, Montserrat Visa, Júlia Rodríguez-Comas, Marcelina Parrizas, Joan Marc Servitja, Anna Novials

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13 Cites (Scopus)

Resum

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.

Idioma originalAnglès
Pàgines (de-a)57-65
Nombre de pàgines9
RevistaMolecular and Cellular Endocrinology
Volum420
DOIs
Estat de la publicacióPublicada - 15 de gen. 2016
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