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mTORC1-Independent Reduction of Retinal Protein Synthesis in Type 1 Diabetes
- Source :
- Diabetes
- Publication Year :
- 2014
- Publisher :
- American Diabetes Association, 2014.
-
Abstract
- Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2Akita diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended 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 with muscle and liver that may provide a new means to ameliorate diabetic retinopathy.
- Subjects :
- Blood Glucose
Male
Complications
Endocrinology, Diabetes and Metabolism
mTORC1
mTORC2
Mice
chemistry.chemical_compound
0302 clinical medicine
beta-Crystallin B Chain
Insulin
0303 health sciences
TOR Serine-Threonine Kinases
Intracellular Signaling Peptides and Proteins
medicine.anatomical_structure
medicine.medical_specialty
P70-S6 Kinase 1
Mechanistic Target of Rapamycin Complex 2
Biology
Protein degradation
alpha-Crystallin A Chain
Retina
Diabetes Mellitus, Experimental
03 medical and health sciences
Internal medicine
Internal Medicine
medicine
Animals
Eye Proteins
Protein kinase B
030304 developmental biology
Protein turnover
Skeletal muscle
Retinal
Regulatory-Associated Protein of mTOR
Phosphoproteins
Receptor, Insulin
Rats
Diabetes Mellitus, Type 1
Phlorhizin
Rapamycin-Insensitive Companion of mTOR Protein
Endocrinology
chemistry
RNA, Ribosomal
Hyperglycemia
Multiprotein Complexes
Protein Biosynthesis
030221 ophthalmology & optometry
Carrier Proteins
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....3c73480949dbdeea316d905389b22b3c
- Full Text :
- https://doi.org/10.2337/db14-0235