TY - JOUR
T1 - Peroxiredoxin 6, a novel player in the pathogenesis of diabetes
AU - Pacifici, Francesca
AU - Arriga, Roberto
AU - Sorice, Gian Pio
AU - Capuani, Barbara
AU - Scioli, Maria Giovanna
AU - Pastore, Donatella
AU - Donadel, Giulia
AU - Bellia, Alfonso
AU - Caratelli, Sara
AU - Coppola, Andrea
AU - Ferrelli, Francesca
AU - Federici, Massimo
AU - Sconocchia, Giuseppe
AU - Tesauro, Manfredi
AU - Sbraccia, Paolo
AU - Della-Morte, David
AU - Giaccari, Andrea
AU - Orlandi, Augusto
AU - Lauro, Davide
N1 - Publisher Copyright:
© 2014 by the American Diabetes Association.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
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U2 - 10.2337/db14-0144
DO - 10.2337/db14-0144
M3 - Article
C2 - 24947358
AN - SCOPUS:84907494213
VL - 63
SP - 3210
EP - 3220
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 10
ER -