The expression of TNF alpha by human muscle. Relationship to insulin resistance

TNFalpha is orverexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. U...

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Bibliographic Details
Published in:The Journal of clinical investigation 1996-02, Vol.97 (4), p.1111-1116
Main Authors: Saghizadeh, M, Ong, J M, Garvey, W T, Henry, R R, Kern, P A
Format: Article
Language:English
Subjects:
Adult
Animals
Base Sequence
Cells, Cultured
Diabetes Mellitus - metabolism
DNA Primers - chemistry
Gene Expression
Humans
Insulin Resistance
Molecular Sequence Data
Muscles - metabolism
Obesity - metabolism
Rats
RNA, Messenger - genetics
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
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Summary:TNFalpha is orverexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. Using RT-PCR, TNF was detected in human heart, in skeletal muscle from humans and rats, and in cultured human myocytes. Using competitive RT-PCR, TNF was quantitated in the muscle biopsy specimens from 15 subjects whose insulin sensitivity had been characterized using the glucose clamp. technique. TNF expression in the insulin resistant subjects and the diabetic patients was fourfold higher than in the insulin sensitive subjects, and there was a significant inverse linear relationship between maximal glucose disposal rate and muscle TNF (r = -0.60, P < 0.02). In nine subjects, muscle cells from vastus lateralis muscle biopsies were placed into tissue culture for 4 wk, and induced to differentiate into myotubes. TNF was secreted into the medium from these cells, and cells from diabetic patients expressed threefold more TNF than cells from nondiabetic subjects. Thus, TNF is expressed in human muscle, and is expressed at a higher level in the muscle tissue and in the cultured muscle cells from insulin resistant and diabetic subjects. These data suggest another mechanism by which TNF may play an important role in human insulin resistance.
ISSN:0021-9738
DOI:10.1172/jci118504