Long-term treatment with insulin induces apoptosis in brown adipocytes: role of oxidative stress
Autor: | Manuel Benito, Blanca Herrera, Isabel Fabregat, Alberto Alvarez, Almudena Porras, Amparo Valladares, Susana Zuluaga |
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Přispěvatelé: | Universitat de Barcelona |
Jazyk: | angličtina |
Rok vydání: | 2003 |
Předmět: |
medicine.medical_specialty
Estrès oxidatiu medicine.medical_treatment Adipose tissue Caspase 3 Apoptosis Biology Caspase 8 Antioxidants Endocrinology Insulin resistance Adipose Tissue Brown Internal medicine Insulina Brown adipose tissue medicine Adipocytes Animals Hypoglycemic Agents Insulin Enzyme Inhibitors Cells Cultured Phosphoinositide-3 Kinase Inhibitors Sirolimus Antibiotics Antineoplastic Cytochrome c Apoptosi Adipose tissues medicine.disease Caspase 9 Rats Insulin receptor Oxidative Stress Teixit adipós medicine.anatomical_structure Oxidative stress Caspases Culture Media Conditioned biology.protein |
Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname |
Popis: | Trying to define the precise role played by insulin regulating the survival of brown adipocytes, we have used rat fetal brown adipocytes maintained in primary culture. The effect of insulin on apoptosis and the mechanisms involved were assessed. Different from the known effects of insulin as a survival factor, we have found that long-term treatment (72 h) with insulin induces apoptosis in rat fetal brown adipocytes. This process is dependent on the phosphatidylinositol 3-kinase/mammalian target of rapamycin/p70 S6 kinase pathway. Short-term treatment with the conditioned medium from brown adipocytes treated with insulin for 72 h mimicked the apoptotic effect of insulin. During the process, caspase 8 activation, Bid cleavage, cytochrome c release, and activation of caspases 9 and 3 are sequentially produced. Treatment with the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (Z-VAD), prevents activation of this apoptotic cascade. The antioxidants, ascorbic acid and superoxide dismutase, also impair this process of apoptosis. Moreover, generation of reactive oxygen species (ROS), probably through reduced nicotinamide adenine dinucleotide phosphate oxidases, and a late decrease in reduced glutathione content are produced. According to this, antioxidants prevent caspase 8 activation and Bid cleavage, suggesting that ROS production is an important event mediating this process of apoptosis. However, the participation of uncoupling protein-1, -2, and -3 regulating ROS is unclear because their levels remain unchanged upon insulin treatment for 72 h. Our data suggest that the prolonged hyperinsulinemia might cause insulin resistance through the loss of brown adipose tissue. |
Databáze: | OpenAIRE |
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