Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

  1. Davide Lauro1
  1. 1Department of System Medicine, University of Rome Tor Vergata, Italy
  2. 2Division of Endocrinology and Metabolic Diseases, Università Cattolica del Sacro Cuore, Rome, Italy
  3. 3Diabetic Care Clinics, Associazione Cavalieri Italiani Sovrano Militare Ordine Di Malta, Rome, Italy
  4. 4Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy
  5. 5Institute of Translational Pharmacology, National Research Council, Rome, Italy
  6. 6Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy
  7. 7Fondazione Don Gnocchi, Milan, Italy
  1. Corresponding author: Davide Lauro, d.lauro{at}med.uniroma2.it.
  1. F.P. and R.A. contributed equally to this work.

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.

  • Received January 27, 2014.
  • Accepted April 28, 2014.

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  1. Diabetes
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