Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/12674
Title: Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress
Authors: Duarte, Ana I. 
Proença, Teresa 
Oliveira, Catarina R. 
Santos, Maria S. 
Rego, A. Cristina 
Issue Date: Oct-2006
Publisher: American Diabetes Association
Citation: Diabetes. 55:10 (2006) 2863-2870
Abstract: We previously demonstrated that insulin has a neuroprotective role against oxidative stress, a deleterious condition associated with diabetes, ischemia, and age-related neurodegenerative diseases. In this study, we investigated the effect of insulin on neuronal glucose uptake and metabolism after oxidative stress in rat primary cortical neurons. On oxidative stress, insulin stimulates neuronal glucose uptake and subsequent metabolism into pyruvate, restoring intracellular ATP and phosphocreatine. Insulin also increases intracellular and decreases extracellular adenosine, counteracting the effect of oxidative stress. Insulin effects are apparently mediated by phosphatidylinositol 3-K and extracellular signal-regulated kinase signaling pathways. Extracellular adenosine under oxidative stress is largely inhibited after blockade of ecto-5'-nucleotidase, suggesting that extracellular adenosine results preferentially from ATP release and catabolism. Moreover, insulin appears to interfere with the ATP release induced by oxidative stress, regulating extracellular adenosine levels. In conclusion, insulin neuroprotection against oxidative stress-mediated damage involves 1) stimulation of glucose uptake and metabolism, increasing energy levels and intracellular adenosine and, ultimately, uric acid formation and 2) a decrease in extracellular adenosine, which may reduce the facilitatory activity of adenosine receptors
URI: http://hdl.handle.net/10316/12674
ISSN: 0012-1797
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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