Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration
| Autor: | Anderson C, Marçal, Mauro, Leonelli, Jarlei, Fiamoncini, Francisco C, Deschamps, Maria A M, Rodrigues, Rui, Curi, Angelo R, Carpinelli, Luiz R G, Britto, Carla R O, Carvalho |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Male Diabetic Retinopathy Nitric Oxide Synthase Type III Fatty Acids Retinal Degeneration Apoptosis Nitric Oxide Synthase Type I Dietary Fats Lipids Retina Rats Disease Models Animal Phosphatidylinositol 3-Kinases Liver Astrocytes Insulin Receptor Substrate Proteins Animals Lipid Peroxidation Obesity Insulin Resistance Rats Wistar Eye Proteins Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Cell biochemistry and function. 31(1) |
| ISSN: | 1099-0844 |
| Popis: | Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT(1) , eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. |
| Databáze: | OpenAIRE |
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