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 knock-out (-/-) 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.

Pacifici, F., Arriga, R., Sorice, G., Capuani, B., Scioli, M., Pastore, D., et al. (2014). Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. DIABETES, 63(10), 3210-3220 [10.2337/db14-0144].

Peroxiredoxin 6, a novel player in the pathogenesis of diabetes

PACIFICI, FRANCESCA;ARRIGA, ROBERTO;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;ORLANDI, AUGUSTO;LAURO, DAVIDE
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 knock-out (-/-) 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/09 - Medicina Interna
Settore MED/13 - Endocrinologia
Settore MED/08 - Anatomia Patologica
Settore MED/05 - Patologia Clinica
Settore MED/04 - Patologia Generale
English
Con Impact Factor ISI
Animals; Glucose Tolerance Test; Peroxiredoxin VI; Glucose; Islets of Langerhans; Insulin; Blood Glucose; Mice, Knockout; Hyperglycemia; Diabetes Mellitus, Type 2; Oxidative Stress; Insulin Resistance; Female
Pacifici, F., Arriga, R., Sorice, G., Capuani, B., Scioli, M., Pastore, D., et al. (2014). Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. DIABETES, 63(10), 3210-3220 [10.2337/db14-0144].
Pacifici, F; Arriga, R; Sorice, G; Capuani, B; Scioli, Mg; Pastore, D; Donadel, G; Bellia, A; Caratelli, S; Coppola, A; Ferrelli, F; Federici, M; Sconocchia, G; Tesauro, M; Sbraccia, P; DELLA MORTE, D; Giaccari, A; Orlandi, A; Lauro, D
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/88487
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