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: Contribution to journalArticle

36 Scopus citations

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)
Pages (from-to)3210-3220
Number of pages11
JournalDiabetes
Volume63
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Pacifici, F., Arriga, R., Sorice, G. P., Capuani, B., Scioli, M. G., 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. Diabetes, 63(10), 3210-3220. https://doi.org/10.2337/db14-0144