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.