Genes for systemic vascular complications are differentially expressed in the livers of type 2 diabetic patients.
OBJECTIVE
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
These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.
Department of Diabetes and Digestive Disease, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
T
T
Takamura
M
M
Sakurai
T
T
Ota
H
H
Ando
M
M
Honda
S
S
Kaneko
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000503:physiopathology
D016207:Cytokines; D018076:DNA, Complementary; D005456:Fluorescent Dyes; D016372:RNA, Antisense; D012333:RNA, Messenger