Insulin therapy modulates mitochondrial dynamics and biogenesis, autophagy and tau protein phosphorylation in the brain of type 1 diabetic rats.

RX Santos, Sónia C Correia, MG Alves, PF Oliveira, S Cardoso, C Carvalho, AI Duarte, MS Santos, PI Moreira*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The main purpose of this study was to examine whether streptozotocin (STZ)-induced type 1 diabetes (T1D) and insulin (INS) treatment affect mitochondrial function, fission/fusion and biogenesis, autophagy and tau protein phosphorylation in cerebral cortex from diabetic rats treated or not with INS. No significant alterations were observed in mitochondrial function as well as pyruvate levels, despite the significant increase in glucose levels observed in INS-treated diabetic rats. A significant increase in DRP1 protein phosphorylated at Ser616 residue was observed in the brain cortex of STZ rats. Also an increase in NRF2 protein levels and in the number of copies of mtDNA were observed in STZ diabetic rats, these alterations being normalized by INS. A slight decrease in LC3-II levels was observed in INS-treated rats when compared to STZ diabetic animals. An increase in tau protein phosphorylation at Ser396 residue was observed in STZ diabetic rats while INS treatment partially reversed that effect. Accordingly, a modest reduction in the activation of GSK3β and a significant increase in the activity of phosphatase 2A were found in INS-treated rats when compared to STZ diabetic animals. No significant alterations were observed in caspases 9 and 3 activity and synaptophysin and PSD95 levels. Altogether our results show that mitochondrial alterations induced by T1D seem to involve compensation mechanisms since no significant changes in mitochondrial function and synaptic integrity were observed in diabetic animals. In addition, INS treatment is able to normalize the alterations induced by T1D supporting the importance of INS signaling in the brain.
Original languageEnglish
Pages (from-to)1154-1166
Number of pages13
JournalBiochimica et Biophysica Acta
Volume1842
Issue number7
Early online date18 Apr 2014
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Autophagy
  • Cerebal cortex
  • Insulin treatment
  • Tau protein phosphorylation
  • Type 1 diabetes
  • Mitochondrial fission, fusion and biogenesis

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