RRC ID 1587
Author Takamura T, Sakurai M, Ota T, Ando H, Honda M, Kaneko S.
Title Genes for systemic vascular complications are differentially expressed in the livers of type 2 diabetic patients.
Journal Diabetologia
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.
Volume 47(4)
Pages 638-47
Published 2004-4-1
DOI 10.1007/s00125-004-1366-y
PMID 15298340
MeSH Adult Aged Cytokines / metabolism DNA, Complementary / biosynthesis DNA, Complementary / genetics Diabetes Mellitus, Type 2 / genetics* Diabetes Mellitus, Type 2 / pathology Diabetes Mellitus, Type 2 / physiopathology Diabetic Angiopathies / genetics* Diabetic Angiopathies / pathology Diabetic Angiopathies / physiopathology Female Fluorescent Dyes Gene Expression Regulation / physiology* Humans Image Processing, Computer-Assisted Liver / metabolism* Liver / pathology Liver Cirrhosis / pathology Male Middle Aged Multigene Family / genetics Oligonucleotide Array Sequence Analysis RNA, Antisense RNA, Messenger / biosynthesis RNA, Messenger / isolation & purification Reverse Transcriptase Polymerase Chain Reaction Risk Assessment Signal Transduction / genetics Stress, Physiological / physiopathology
IF 7.518
Times Cited 42
DNA material pBlue hNF-IL6 (610 Sal I) (RDB01314) Transforming growth factor beta receptor type IIB (RDB01606)