Genes for systemic vascular complications are differentially expressed in the livers of Type 2 diabetic patients |
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Authors: | T?Takamura M?Sakurai T?Ota H?Ando M?Honda Email author" target="_blank">S?KanekoEmail author |
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Institution: | (1) Department of Diabetes and Digestive Disease, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan |
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Abstract: | Aims/hypothesis Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes.Methods Liver biopsy samples were obtained from twelve patients with Type 2 diabetes and from nine non-diabetic patients. To assay gene expression globally in the livers of both groups, we made complementary DNA (cDNA) microarrays consisting of 1080 human cDNAs. Relative expression ratios of individual genes were obtained by comparing cyanine 5-labelled cDNA from the patients with cyanine 3-labelled cDNA from reference RNA from the liver of a non-diabetic patient.Results On assessing the similarities of differentially expressed genes, the gene expression profiles of the twelve diabetic patients formed a separate cluster from those of the non-diabetic patients. Of the 1080 genes assayed, 105 (9.7%) were up-regulated and 134 (12%) were down-regulated in the diabetic livers (p<0.005). The genes up-regulated in the diabetic patients included those encoding angiogenic factors such as vascular endothelial growth factor, endothelin and platelet-derived growth factor. They also included TGF superfamily genes such as TGFA and TGFB1 as well as bone morphogenetic proteins. Among the down-regulated genes in the diabetic patients were molecules defending against stress, e.g. flavin-containing monooxygenase and superoxide dismutase.Conclusions/interpretation These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.Electronic Supplementary Material Supplementary material is available in the online version of this article at Abbreviations aRNA
antisense RNA
- BMP
bone morphogenetic protein
- cDNA
complementary DNA
- Cy
cyanine
- FMO
flavin-containing monooxygenase
- NASH
non-alcoholic steatohepatitis
- PDGF
platelet-derived growth factor
- SSC
standard saline citrate
- SOD
superoxide dismutase
- VCAM
vascular cell adhesion molecule
- VEGF
vascular endothelial growth factor |
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Keywords: | cDNA microarray Liver Type 2 diabetes Vascular complications |
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