Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients.
Interleukin-6 (IL-6) could be a possible mediator of insulin resistance. We investigated whether IL-6 could inhibit insulin signaling in human skeletal myotubes and whether suppressor of cytokine signaling 3 (SOCS-3) could be related to insulin resistance in vivo in humans. IL-6 inhibited insulin signaling and induced SOCS-3 expression in differentiated myotubes. SOCS-3 mRNA levels were significantly increased in the skeletal muscle of type 2 diabetic patients compared with control subjects and correlated with reduced insulin-stimulated glucose uptake. In contrast, SOCS-3 mRNA levels were reduced in muscle of obese nondiabetic subjects compared with type 2 diabetic patients, despite similar circulating concentrations of IL-6. Increased SOCS-3 mRNA levels in diabetes were not attributable to hyperglycemia, as type 1 diabetic patients had normal SOCS-3 mRNA expression in muscle. However, the combination of high glucose and IL-6 levels in type 2 diabetic patients may induce SOCS-3 expression, as has been seen in human muscle cells. In subcutaneous adipose tissue, SOCS-3 mRNA levels were increased in obese individuals and strongly correlated with IL-6 expression, supporting a paracrine effect of IL-6 on SOCS-3 expression in fat. Taken together, our results showed that SOCS-3 expression in human skeletal muscle in vivo is not related to insulin resistance in the presence of elevated IL-6 concentrations and suggest that cytokine action could differ in type 2 diabetic patients and nondiabetic obese subjects.
INSERM U449/INRA U1235, Faculté de Médecine René Laennec, Rue G. Paradin, F-69372 Lyon, Cedex 08, France. jennifer.rieusset@univ-lyon1.fr
Jennifer
J
Rieusset
Karim
K
Bouzakri
Emmanuel
E
Chevillotte
Nadège
N
Ricard
Delphine
D
Jacquet
Jean-Philippe
JP
Bastard
Martine
M
Laville
Hubert
H
Vidal
D000273:Adipose Tissue / Q000502:physiology; D000328:Adult; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009765:Obesity; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D015850:Interleukin-6; D012333:RNA, Messenger; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors