Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass due to a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes in spite of reduced Akt activity and enhanced cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than other insulin-sensitive tissues such as skeletal muscle. Ins2Akita diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions of retinal protein synthesis matched by concomitant reduction of retinal protein degradation, associated with preserved retinal mass and protein content. The reduction in protein synthesis was dependent on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but surprisingly not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared to muscle and liver that may provide new means to ameliorate diabetic retinopathy.
- Received February 11, 2014.
- Accepted April 9, 2014.
- © 2014 by the American Diabetes Association.
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