Microarray profiling of human skeletal muscle reveals that insulin regulates approximately 800 genes during a hyperinsulinemic clamp.
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.
Rome
Sophie
S
INSERM U.449 and Human Nutrition Research Center of Lyon, Faculty of Medicine R. Laennec, Lyon Cédex 08, France. srome@univ-lyon1.fr
Clément
Karine
K
Rabasa-Lhoret
Rémi
R
Loizon
Emmanuelle
E
Poitou
Christine
C
Barsh
Greg S
GS
Riou
Jean-Paul
JP
Laville
Martine
M
Vidal
Hubert
H
D000328:Adult; D001692:Biological Transport; D003546:Cysteine Endopeptidases / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation
D018076:DNA, Complementary; D007328:Insulin; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D025801:Ubiquitin; D012313:RNA; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex