Genetic disruption of SOD1 gene causes glucose intolerance and impairs β-cell function

Andrea Giaccari, Giovanna Muscogiuri, Adam B. Salmon, Cristina Aguayo-Mazzucato, Mengyao Li, Bogdan Balas, Rodolfo Guardado-Mendoza, Robert L. Reddick, Sara M. Reyna, Gordon Weir, Ralph A. Defronzo, Holly Van Remmen, Nicolas Musi

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19 Citazioni (Scopus)

Abstract

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction.
Lingua originaleEnglish
pagine (da-a)4201-4207
Numero di pagine7
RivistaDiabetes
Volume62
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • Animals
  • Blood Glucose
  • Diet, High-Fat
  • Glucose Intolerance
  • Glucose Tolerance Test
  • Insulin
  • Insulin Resistance
  • Insulin-Secreting Cells
  • Mice, Knockout
  • Oxidative Stress
  • Superoxide Dismutase
  • cellule secernenti insulina
  • dieta iperlipidica
  • insulina
  • insulino-resistenza
  • metabolismo glucidico
  • modello animale
  • stress ossidativo
  • superossido dismutasi
  • test di tolleranza glucidica
  • tolleranza glucidica

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