Journal of Bioenergetics and Biomembranes

, Volume 45, Issue 4, pp 397–407 | Cite as

UCP2 and ANT differently modulate proton-leak in brain mitochondria of long-term hyperglycemic and recurrent hypoglycemic rats

  • Susana Cardoso
  • Maria S. Santos
  • António Moreno
  • Paula I. Moreira


A growing body of evidence suggests that mitochondrial proton-leak functions as a regulator of reactive oxygen species production and its modulation may limit oxidative injury to tissues. The main purpose of this work was to characterize the proton-leak of brain cortical mitochondria from long-term hyperglycemic and insulin-induced recurrent hypoglycemic rats through the modulation of the uncoupling protein 2 (UCP2) and adenine nucleotide translocator (ANT). Streptozotocin-induced diabetic rats were treated subcutaneously with twice-daily insulin injections during 2 weeks to induce the hypoglycemic episodes. No differences in the basal proton-leak, UCP2 and ANT protein levels were observed between the experimental groups. Mitochondria from recurrent hypoglycemic rats presented a decrease in proton-leak in the presence of GDP, a specific UCP2 inhibitor, while an increase in proton-leak was observed in the presence of linoleic acid, a proton-leak activator, this effect being reverted by the simultaneous addition of GDP. Mitochondria from long-term hyperglycemic rats showed an enhanced susceptibility to ANT modulation as demonstrated by the complete inhibition of basal and linoleic acid-induced proton-leak caused by the ANT specific inhibitor carboxyatractyloside. Our results show that recurrent-hypoglycemia renders mitochondria more susceptible to UCPs modulation while the proton-leak of long-term hyperglycemic rats is mainly modulated by ANT, which suggest that brain cortical mitochondria have distinct adaptation mechanisms in face of different metabolic insults.


ANT Cortical brain mitochondria Long-term hyperglycemia Proton-leak Recurrent hypoglycemia UCP2 


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Susana Cardoso
    • 1
    • 2
  • Maria S. Santos
    • 1
    • 2
  • António Moreno
    • 1
    • 2
    • 3
  • Paula I. Moreira
    • 1
    • 4
  1. 1.Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  2. 2.Department of Life Sciences – Faculty of Sciences and TechnologyUniversity of CoimbraCoimbraPortugal
  3. 3.Institute of Marine ResearchUniversity of CoimbraCoimbraPortugal
  4. 4.Laboratory of Physiology, Faculty of MedicineUniversity of CoimbraCoimbraPortugal

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