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Protein disulfide isomerase ameliorates β-cell dysfunction in pancreatic islets overexpressing human islet amyloid polypeptide
- Source :
- Molecular and Cellular Endocrinology. 420:57-65
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- Male
0301 basic medicine
Amyloid
medicine.medical_specialty
medicine.medical_treatment
Palmitic Acid
Protein Disulfide-Isomerases
Apoptosis
Mice, Transgenic
Plasma protein binding
Biology
Biochemistry
03 medical and health sciences
Endocrinology
Transduction, Genetic
Insulin-Secreting Cells
Internal medicine
Insulin Secretion
medicine
Animals
Humans
Insulin
Protein disulfide-isomerase
Molecular Biology
geography
geography.geographical_feature_category
Tissue Extracts
Pancreatic islets
Endoplasmic reticulum
Islet
Islet Amyloid Polypeptide
Glucose
030104 developmental biology
medicine.anatomical_structure
Molecular Chaperones
Protein Binding
Subjects
Details
- ISSN :
- 03037207
- Volume :
- 420
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Endocrinology
- Accession number :
- edsair.doi.dedup.....99f5c8dd04fc5a586adf4e59e71bbfa4