Peroxiredoxin 6, a novel player in the pathogenesis of diabetes

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

Research output: Chapter in Book/Report/Conference proceedingChapter

30 Citations (Scopus)

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 languageEnglish (US)
Title of host publicationDiabetes
PublisherAmerican Diabetes Association Inc.
Pages3210-3220
Number of pages11
Volume63
Edition10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Fingerprint

Peroxiredoxin VI
Insulin
Type 2 Diabetes Mellitus
Glucose
Insulin Resistance
Lipids
Peroxynitrous Acid
Glucose Clamp Technique
Peroxides
Diabetes Complications
Glucose Tolerance Test
Islets of Langerhans
Knockout Mice
Hyperglycemia
Hydrogen Peroxide
Oxidation-Reduction
Phospholipids
Oxidative Stress
Phenotype
Muscles

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Pacifici, F., Arriga, R., Sorice, G. P., Capuani, B., Scioli, M. G., Pastore, D., ... Lauro, D. (2014). Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. In Diabetes (10 ed., Vol. 63, pp. 3210-3220). American Diabetes Association Inc.. https://doi.org/10.2337/db14-0144

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 proceedingChapter

Pacifici, F, Arriga, R, Sorice, GP, 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 2014, Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. in Diabetes. 10 edn, vol. 63, American Diabetes Association Inc., pp. 3210-3220. https://doi.org/10.2337/db14-0144
Pacifici F, Arriga R, Sorice GP, Capuani B, Scioli MG, Pastore D et al. Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. In Diabetes. 10 ed. Vol. 63. American Diabetes Association Inc. 2014. p. 3210-3220 https://doi.org/10.2337/db14-0144
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. / Peroxiredoxin 6, a novel player in the pathogenesis of diabetes. Diabetes. Vol. 63 10. ed. American Diabetes Association Inc., 2014. pp. 3210-3220
@inbook{7b2d2c8e010643d28afa57a3b78f39d7,
title = "Peroxiredoxin 6, a novel player in the pathogenesis of diabetes",
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.",
author = "Francesca Pacifici and Roberto Arriga and Sorice, {Gian Pio} and Barbara Capuani and Scioli, {Maria Giovanna} and Donatella Pastore and Giulia Donadel and Alfonso Bellia and Sara Caratelli and Andrea Coppola and Francesca Ferrelli and Massimo Federici and Giuseppe Sconocchia and Manfredi Tesauro and Paolo Sbraccia and {Della Morte}, David and Andrea Giaccari and Augusto Orlandi and Davide Lauro",
year = "2014",
month = "10",
day = "1",
doi = "10.2337/db14-0144",
language = "English (US)",
volume = "63",
pages = "3210--3220",
booktitle = "Diabetes",
publisher = "American Diabetes Association Inc.",
edition = "10",

}

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 -