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GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through
GLP-1R-ERK1/2-HDAC6 Signaling Pathway
#MMPMID29104476
Cai X
; Li J
; Wang M
; She M
; Tang Y
; Li J
; Li H
; Hui H
Int J Med Sci
2017[]; 14
(12
): 1203-1212
PMID29104476
show ga
Objective: Apoptosis and autophagy of retinal cells, which may be induced by
oxidative stress, are tightly associated with the pathogenesis of diabetic
retinopathy (DR). The autophagy induced by oxidative stress is considered as
excessively stimulated autophagy, which accelerates the progression of DR. This
study aims to investigate the protective effect of GLP-1 treatment on alleviating
apoptosis and autophagy of retinal cells in type 2 diabetic rats and reveals its
possible mechanism. Methods: Type 2 diabetic rats were induced by fed with high
sugar, high fat diet and followed with streptozotocin injection. GLP-1 was
applied to treat the diabetic rats for one week after the onset of diabetes. The
expressions of oxidative stress-related enzymes, retinal GLP-1R,
mitochondria-dependent apoptosis- related genes, autophagy markers, and
autophagy-associated pathway genes were studied by Western blotting or
immunohistochemistry analysis. Results: GLP-1treatment reduced the levels of NOX3
and SOD2 in DR. The expression of BCL2 was increased, while the levels of
caspase3 and LC3B were reduced through GLP-1 treatment in DR. GLP-1 treatment
restored the GLP-1R expression and decreased the levels of phosphorylated AKT and
phosphorylated ERK1/2, which was accompanied with the reduction of the HDAC6
levels in DR. Conclusions: GLP-1 treatment can alleviate autophagy which may be
induced by oxidative stress; this protective effect is likely through
GLP-1R-ERK1/2-HDAC6 signaling pathway.
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