TY - JOUR
T1 - Expression profiling of insulin action in human myotubes
T2 - induction of inflammatory and pro-angiogenic pathways in relationship with glycogen synthesis and type 2 diabetes
AU - Hansen, Lars
AU - Gaster, Michael
AU - Oakeley, Edward J
AU - Brusgaard, Klaus
AU - Damsgaard Nielsen, Eva-Maria
AU - Beck-Nielsen, Henning
AU - Pedersen, Oluf
AU - Hemmings, Brian A
N1 - Copyright 2004 Elsevier Inc.
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - Adult
KW - Cells, Cultured
KW - Cytokines
KW - Diabetes Mellitus, Type 2
KW - Dose-Response Relationship, Drug
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Glycogen
KW - Humans
KW - Inflammation
KW - Insulin
KW - Insulin Resistance
KW - Kinetics
KW - Male
KW - Middle Aged
KW - Muscle Fibers, Skeletal
KW - Muscle, Skeletal
KW - Neovascularization, Pathologic
KW - Oligonucleotide Array Sequence Analysis
KW - Signal Transduction
U2 - 10.1016/j.bbrc.2004.08.146
DO - 10.1016/j.bbrc.2004.08.146
M3 - Journal article
C2 - 15369805
SN - 0006-291X
VL - 323
SP - 685
EP - 695
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
