Acute hyperglycemia induces a global downregulation of gene expression in adipose tissue and skeletal muscle of healthy subjects.
To define the effects of acute hyperglycemia per se (i.e., without the confounding effect of hyperinsulinemia) in human tissues in vivo, we performed global gene expression analysis using microarrays in vastus lateralis muscle and subcutaneous abdominal adipose tissue of seven healthy men during a hyperglycemic-euinsulinemic clamp with infusion of somatostatin to inhibit endogenous insulin release. We found that doubling fasting blood glucose values while maintaining plasma insulin in the fasting range modifies the expression of 316 genes in skeletal muscle and 336 genes in adipose tissue. More than 80% of them were downregulated during the clamp, indicating a drastic effect of acute high glucose, in the absence of insulin, on mRNA levels in human fat and muscle tissues. Almost all the biological pathways were affected, suggesting a generalized effect of hyperglycemia. The induction of genes from the metallothionein family, related to detoxification and free radical scavenging, indicated that hyperglycemia-induced oxidative stress could be involved in the observed modifications. Because the duration and the concentration of the experimental hyperglycemia were close to what is observed during a postprandial glucose excursion in diabetic patients, these data suggest that modifications of gene expression could be an additional effect of glucose toxicity in vivo.
Meugnier
Emmanuelle
E
UMR INSERM870/INRA1235, Faculté de Médecine R. Laennec, Rue G. Paradin, F-69372 Lyon Cedex 08, France.
Faraj
May
M
Rome
Sophie
S
Beauregard
Geneviève
G
Michaut
Angélique
A
Pelloux
Véronique
V
Chiasson
Jean-Louis
JL
Laville
Martine
M
Clement
Karine
K
Vidal
Hubert
H
Rabasa-Lhoret
Rémi
R
D000208:Acute Disease; D000273:Adipose Tissue / Q000502:physiology*; D000328:Adult; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values
D007328:Insulin; D012333:RNA, Messenger