Abstract：
BACKGROUND:Clinical studies have shown that proinsulin C-peptide exerts renoprotective effects in type 1 diabetes, although the underlying mechanisms are poorly understood. As C-peptide has been shown to induce several intracellular events and to localize to nuclei, we aimed to determine whether gene transcription is affected in proximal tubular kidney cells, and if so, whether the genes with altered transcription include those related to protective mechanisms. METHODS:The effect of C-peptide incubation (2 h) on gene expression was investigated in freshly isolated proximal tubular cells from streptozotocin-diabetic Sprague-Dawley rats using global gene expression profiling and real-time quantitative polymerase chain reaction. Protein expression was assayed using western blotting. Different bioinformatic strategies were employed. RESULTS:Gene transcription profiling demonstrated differential transcription of 492 genes (p < 0.01) after 2 h of C-peptide exposure, with the majority of these genes repressed (83%). Real-time quantitative polymerase chain reaction validation supported a trend of several G protein-coupled receptors being activated, and certain transcription factors being repressed. Also, C-peptide repressed the transcription of genes associated with the pathways of circulatory and inflammatory diseases. CONCLUSION:This study shows that C-peptide exerts early effects on gene transcription in proximal tubular cells. The findings also bring further knowledge to the renoprotective mechanisms of C-peptide in type 1 diabetes, and support a transcriptional activity for C-peptide. It is suggested that C-peptide may play a regulatory role in the gene expression of proximal tubular cells.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Lindahl E,Nordquist L,Müller P,El Agha E,Friederich M,Dahlman-Wright K,Palm F,Jörnvall Hdoi
10.1002/dmrr.1220subject
Has Abstractpub_date
2011-10-01 00:00:00pages
697-704issue
7eissn
1520-7552issn
1520-7560journal_volume
27pub_type
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