Document Detail

Uncovering the beginning of diabetes: the cellular redox status and oxidative stress as starting players in hyperglycemic damage.
MedLine Citation:
PMID:  23292031     Owner:  NLM     Status:  Publisher    
Early hyperglycemic insult can lead to permanent, cumulative damage that might be one of the earliest causes for a pre-diabetic situation. Despite this, the early phases of hyperglycemic exposure have been poorly studied. We have previously demonstrated that mitochondrial injury takes place early on upon hyperglycemic exposure. In this work, we demonstrate that just 1 h of hyperglycemic exposure is sufficient to induce increased mitochondrial membrane potential and generation. This is accompanied (and probably caused) by a decrease in the cells' NAD(+)/NADH ratio. Furthermore, we show that the modulation of the activity of parallel pathways to glycolysis can alter the effects of hyperglycemic exposure. Activation of the pentose phosphate pathway leads to diminished effects of glucose on the above parameters, either by removing glucose from glycolysis or by NADPH generation. We also demonstrate that the hexosamine pathway inhibition also leads to a decreased effect of excess glucose. So, this work demonstrates the need for increased focus of study on the reductive status of the cell as one of the most important hallmarks of initial hyperglycemic damage.
João Soeiro Teodoro; Ana Patrícia Gomes; Ana Teresa Varela; Filipe Valente Duarte; Anabela Pinto Rolo; Carlos Marques Palmeira
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  -     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Faculty of Science and Technology, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
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