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Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes
- Source :
- Diabetes (N.Y.N.Y.) 63 (2014): 3210–3220. doi:10.2337/db14-0144, info:cnr-pdr/source/autori:Pacifici, Francesca; Arriga, Roberto; Sorice, Gian Pio; Capuani, Barbara; Scioli, Maria Giovanna; Pastore, Donatella; Donadel, Giulia; Bellia, Alfonso; Caratelli, Sara; Coppola, Andrea; Ferrelli, Francesca; Federici, Massimo; Sconocchia, Giuseppe; Tesauro, Manfredi; Sbraccia, Paolo; Della-Morte, David; Giaccari, Andrea; Orlandi, Augusto; Lauro, Davide/titolo:Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes/doi:10.2337%2Fdb14-0144/rivista:Diabetes (N.Y.N.Y.)/anno:2014/pagina_da:3210/pagina_a:3220/intervallo_pagine:3210–3220/volume:63
- Publication Year :
- 2014
- Publisher :
- American Diabetes Association, 2014.
-
Abstract
- Enhanced oxidative stress contributes to the pathogenesis of diabetes and its complications. Peroxiredoxin 6 (PRDX6) is a key regulator of cellular redox balance, with the peculiar ability to neutralize peroxides, peroxynitrite, and phospholipid hydroperoxides. In the current study, we aimed to define the role of PRDX6 in the pathophysiology of type 2 diabetes (T2D) using PRDX6 knockout (−/−) mice. Glucose and insulin responses were evaluated respectively by intraperitoneal glucose and insulin tolerance tests. Peripheral insulin sensitivity was analyzed by euglycemic-hyperinsulinemic clamp, and molecular tools were used to investigate insulin signaling. Moreover, inflammatory and lipid parameters were evaluated. We demonstrated that PRDX6−/− mice developed a phenotype similar to early-stage T2D caused by both reduced glucose-dependent insulin secretion and increased insulin resistance. Impaired insulin signaling was present in PRDX6−/− mice, leading to reduction of muscle glucose uptake. Morphological and ultrastructural changes were observed in islets of Langerhans and livers of mutant animals, as well as altered plasma lipid profiles and inflammatory parameters. In conclusion, we demonstrated that PRDX6 is a key mediator of overt hyperglycemia in T2D glucose metabolism, opening new perspectives for targeted therapeutic strategies in diabetes care.
- Subjects :
- Blood Glucose
Settore MED/09 - Medicina Interna
Peroxiredoxin 6
diabete mellito
Endocrinology, Diabetes and Metabolism
Glucose uptake
medicine.medical_treatment
Type 2 diabetes
Animals
Glucose Tolerance Test
Peroxiredoxin VI
Glucose
Islets of Langerhans
Insulin
Mice, Knockout
Hyperglycemia
Diabetes Mellitus, Type 2
Oxidative Stress
Insulin Resistance
Female
Mice
insulin resistance
Glucose tolerance test
diabetes
biology
medicine.diagnostic_test
pexiredoxina 6
Type 2
medicine.medical_specialty
Knockout
glucose metabolism
Settore MED/08 - Anatomia Patologica
insulino-resistenza
Carbohydrate metabolism
PRDX6
Insulin resistance
Diabetes mellitus
Internal medicine
Diabetes Mellitus
Internal Medicine
medicine
Settore MED/05 - Patologia Clinica
Settore MED/04 - Patologia Generale
Settore MED/13 - ENDOCRINOLOGIA
bilancio ossidativo cellulare
medicine.disease
Insulin receptor
Endocrinology
biology.protein
diabetes care
cellular redox balance
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....180bde5731c9a7bae85add7ae9cf7b29
- Full Text :
- https://doi.org/10.2337/db14-0144