mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes.
Authors Fort PE, Losiewicz MK, Pennathur S, Jefferson LS, Kimball SR, Abcouwer SF,
Gardner TW
Submitted By Submitted Externally on 6/2/2014
Status Published
Journal Diabetes
Year 2014
Date Published 4/16/2014
Volume : Pages 63 : 3077 - 3090
PubMed Reference 24740573
Abstract 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. Ins2(Akita) 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.

Investigators with authorship
Steven AbcouwerUniversity of Michigan-Ann Arbor