METABOLISM AND BIOENERGETICS
Microarray Profiling of Human Skeletal Muscle Reveals That Insulin Regulates ∼800 Genes during a Hyperinsulinemic Clamp*210

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Insulin action in target tissues involved precise regulation of gene expression. To define the set of insulin-regulated genes in human skeletal muscle, we analyzed the global changes in mRNA levels during a 3-h hyperinsulinemic euglycemic clamp in vastus lateralis muscle of six healthy subjects. Using 29,308 cDNA element microarrays, we found that the mRNA expression of 762 genes, including 353 expressed sequence tags, was significantly modified during insulin infusion. 478 were up-regulated and 284 down-regulated. Most of the genes with known function are novel targets of insulin. They are involved in the transcriptional and translational regulation (29%), intermediary and energy metabolisms (14%), intracellular signaling (12%), and cytoskeleton and vesicle traffic (9%). Other categories consisted of genes coding for receptors, carriers, and transporters (8%), components of the ubiquitin/proteasome pathways (7%) and elements of the immune response (5.5%). These results thus define a transcriptional signature of insulin action in human skeletal muscle. They will help to better define the mechanisms involved in the reduction of insulin effectiveness in pathologies such as type 2 diabetes mellitus, a disease characterized by defective regulation of gene expression in response to insulin.

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Published, JBC Papers in Press, March 5, 2003, DOI 10.1074/jbc.M300293200

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This work was supported in part by INSERM Action Thématique concertée Nutrition Grant 4NU10G and by grants from the Institut de Recherche Servier, Région Rhône-Alpes, and Claude Bernard Fondation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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The on-line version of this article (available athttp://www.jbc.org) contains a supplemental table.