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H. Imai, M. K. Losiewicz, R. Goel, P. E. Fort, T. W. Gardner; Insulin-Like Growth Factor 2 (IGF2) is Reduced in Diabetic Retina and Serum. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5093.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the expression pattern of IGF2 isoforms in diabetic rat tissues and serum, and in serum of patients with Type 1 diabetees and retinopathy.
For in vivo experiments, retinas and serum were extracted from streptozotocin induced 12 week diabetic male Sprague-Dawley rats and used for the western blot (WB) for IGF2. For ex vivo experiments, retinas were extracted from normal rats and incubated for 15min with or without mature-, big-, or pro-IGF2 (1-100nM). WB and immunoprecipitation were performed to assess the effect of each IGF2 isoform on insulin receptor (IR) and IGF1 receptor (IGF1R) autophosphorylation. For in vitro experiments, differentiated R28 cells were serum-deprived for 6 hours with or without treatment by recombinant IGF2 isoforms (1-100nM). WB, caspase-3 activity assay and DNA fragmentation ELISA were performed to check the anti-apoptotic effect of each IGF2 isoform.
In retina, big- and pro-IGF2 levels were reduced in diabetic rat and mature IGF2 was not detected in both normal and diabetic rat. In serum, all IGF2 isoforms were detected and were reduced in diabetic rat. IGF2 treatment significantly increased IR and IGF1R auto-phosphorylation in ex vivo retina and phosphorylation of GSK3beta, P70 6K, mTOR, MAPK and Akt dose-dependently (p<0.01) in vitro. IGF2 significantly decreased caspase-3 activity and DNA fragmentation induced by serum deprivation in vitro. Mature, big- and pro-IGF2 phosphorylated all pro-survival kinases (p<0.01) and decreased caspase-3 and DNA fragmentation.
This data suggest that the reduced retinal and serum IGF2 levels may contribute to the development of neurodegeneration in diabetic retinopathy.
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