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.
| Original language | English (US) |
|---|---|
| Title of host publication | Diabetes |
| Publisher | American Diabetes Association Inc. |
| Pages | 3210-3220 |
| Number of pages | 11 |
| Volume | 63 |
| Edition | 10 |
| DOIs | |
| State | Published - Oct 1 2014 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
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Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. / 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.
Diabetes. Vol. 63 10. ed. American Diabetes Association Inc., 2014. p. 3210-3220.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84907494213&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907494213&partnerID=8YFLogxK
U2 - 10.2337/db14-0144
DO - 10.2337/db14-0144
M3 - Chapter
VL - 63
SP - 3210
EP - 3220
BT - Diabetes
PB - American Diabetes Association Inc.
ER -