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Acute hyperglycemia induces a global down-regulation of gene expression in adipose tissue and in skeletal muscle of healthy subjects

¹INSERM unit 449; INRA unit 1235; Claude Bernard University-Lyon 1, IFR 62, R. Laennec Faculty of Medicine, Lyon, France
²Metabolic Dysfunctions Laboratory, Department of Nutrition, University of Montreal, Montreal, Canada
³INSERM unit 755 Nutriomique; University Pierre and Marie Curie-Paris 6, Faculty of Medicine, Les Cordeliers, France
⁴Research Center, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Canada

Correspondence: vidal{at}sante.univ-lyon1.fr

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 7 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 in adipose tissue. More than 80% of them were down-regulated 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 post-prandial glucose excursion in diabetic patients, these data suggest that modifications of gene expression could be an additional effect of glucose toxicity in vivo.

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