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Ly, A. ; Scheerer, M.F. ; Zukunft, S. ; Muschet, C. ; Merl, J. ; Adamski, J. ; Hrabě de Angelis, M. ; Neschen, S. ; Hauck, S.M. ; Ueffing, M.

Retinal proteome alterations in a mouse model of type 2 diabetes.

Diabetologia 57, 192-203 (2013)
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AIMS/HYPOTHESIS: Diabetic retinopathy is a major complication of type 2 diabetes and the leading cause of blindness in adults of working age. Neuronal defects are known to occur early in disease, but the source of this dysfunction is unknown. The aim of this study was to examine differences in the retinal membrane proteome among non-diabetic mice and mouse models of diabetes either with or without metformin treatment. METHODS: Alterations in the retinal membrane proteome of 10-week-old diabetic db/db mice, diabetic db/db mice orally treated with the anti-hyperglycaemic metformin, and congenic wild-type littermates were examined using label-free mass spectrometry. Pathway enrichment analysis was completed with Genomatix and Ingenuity. Alterations in Slc17a7 mRNA and vesicular glutamate transporter 1 (VGLUT1) protein expression were evaluated using real-time quantitative PCR and immunofluorescence. RESULTS: A total of 98 proteins were significantly differentially abundant between db/db and wild-type animals. Pathway enrichment analysis indicated decreases in levels of proteins related to synaptic transmission and cell signalling. Metformin treatment produced 63 differentially abundant proteins compared with untreated db/db mice, of which only 43 proteins were found to occur in both datasets, suggesting that treatment only partially normalises the alterations induced by diabetes. VGLUT1, which is responsible for loading glutamate into synaptic vesicles, was found to be differentially abundant in db/db mice and was not normalised by metformin. The decrease in Slc17a7/VGLUT1 was confirmed by transcriptomic and immunocytochemical analysis. CONCLUSIONS/INTERPRETATION: These findings expand the knowledge of the protein changes in diabetic retinopathy and suggest that membrane-associated signalling proteins are susceptible to changes that are partially ameliorated by treatment.  
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Publication type Article: Journal article
Document type Scientific Article
Keywords Complex I; Diabetes; Label-free mass spectrometry; Membrane; Metformin; Proteome; Retinopathy; VGLUT1; Vitreous Fluid ; Db/db Mice ; Retinopathy ; Rats ; Metformin ; Pathogenesis ; Dysfunction ; Expression ; Mellitus ; Rod
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 57, Issue: 1, Pages: 192-203 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Institute of Experimental Genetics (IEG)
Molekulare Endokrinologie und Metabolismus (MEM)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30201 - Metabolic Health
90000 - German Center for Diabetes Research
Research field(s) Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-505700-001
G-500600-003
G-500600-001
G-505600-001
G-501900-061
G-501900-062
PubMed ID 24078137
DOI 10.1007/s00125-013-3070-2
WOS ID WOS:000328332900023
Scopus ID 84890894593
Erfassungsdatum 2013-10-01
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