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Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Authors :
Davide Lauro
Francesca Ferrelli
Gian Pio Sorice
Giuseppe Sconocchia
Paolo Sbraccia
Alfonso Bellia
Massimo Federici
David Della-Morte
Donatella Pastore
Francesca Pacifici
Maria Giovanna Scioli
Andrea Coppola
Roberto Arriga
Giulia Donadel
Manfredi Tesauro
Sara Caratelli
Augusto Orlandi
Andrea Giaccari
Barbara Capuani
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.

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