Expression profiling of insulin action in human myotubes: induction of inflammatory and pro-angiogenic pathways in relationship with glycogen synthesis and type 2 diabetes

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Lars Hansen, Michael Gaster, Edward J Oakeley, Klaus Brusgaard, Eva-Maria Damsgaard Nielsen, Henning Beck-Nielsen, Oluf Pedersen, Brian A Hemmings

Myotube cultures from patients with type 2 diabetes mellitus (T2DM) represent an experimental in vitro model of T2DM that offers a possibility to perform gene expression studies under standardized conditions. During a time-course of insulin stimulation (1 microM) at 5.5 mM glucose for 0 (no insulin), 0.5, 1, 2, 4, 8, and 24 h, mRNA contents were analyzed in human myotubes for each time point using Affymetrix DNA chip technology. Insulin treatment induced an inflammatory and pro-angiogenic response in the myotubes, with expression of early response factors followed by inflammatory chemokines, metabolic enzymes, and finally cell cycle regulating genes. One-hundred-forty-four genes were differentially expressed in myotubes from donors with type 2 diabetes compared with control subjects, including HSP70, apolipoprotein D/E, tropomyosin, myosin, and actin previously reported from in vivo studies of diabetic skeletal muscle. We conclude, (i) that insulin induces a time-dependent inflammatory and pro-angiogenic transcriptional response in cultured human myotubes, (ii) that myotubes in vitro retain a gene expression pattern specific for type 2 diabetes and sharing five genes with that of type 2 diabetic skeletal muscle in vivo, and (iii) that insulin, despite similar metabolic effects of glucose uptake and glycogen synthesis, regulates different pools of genes in skeletal muscle during in vivo and in vitro conditions.
Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Volume323
Issue number2
Pages (from-to)685-95
Number of pages11
ISSN0006-291X
DOIs
Publication statusPublished - 2004

    Research areas

  • Adult, Cells, Cultured, Cytokines, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Gene Expression Profiling, Gene Expression Regulation, Glycogen, Humans, Inflammation, Insulin, Insulin Resistance, Kinetics, Male, Middle Aged, Muscle Fibers, Skeletal, Muscle, Skeletal, Neovascularization, Pathologic, Oligonucleotide Array Sequence Analysis, Signal Transduction

ID: 38457238