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.
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pacifici
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Arriga
authors.affiliation: Division of Endocrinology and Metabolic Diseases, Università Cattolica del Sacro Cuore, Rome, Italy Diabetic Care Clinics, Associazione dei Cavalieri Italiani Sovrano Militare Ordine di Malta, Rome, Italy.
authors.forename: Gian Pio
authors.initials: GP
authors.lastname: Sorice
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Capuani
authors.affiliation: Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Scioli
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Pastore
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Donadel
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bellia
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy Institute of Translational Pharmacology, National Research Council, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caratelli
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrelli
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy Institute of Translational Pharmacology, National Research Council, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sconocchia
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sbraccia
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
authors.affiliation: Division of Endocrinology and Metabolic Diseases, Università Cattolica del Sacro Cuore, Rome, Italy Fondazione Don Carlo Gnocchi, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giaccari
authors.affiliation: Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Department of System Medicine, University of Rome Tor Vergata, Rome, Italy d.lauro@med.uniroma2.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism*; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse; D005947:Glucose