The expression of TNF alpha by human muscle. Relationship to insulin resistance.
Open accessAbstract
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.
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Elevated TNFα mRNA and protein levels have been detected in human obesity.
“Elevated TNF␣ mRNA and protein levels have also been detected in human obesity (51,52).”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [52]
The Introduction reports elevated TNF expression in adipose tissue from obese humans, and the Results report higher muscle TNF mRNA in insulin-resistant and diabetic subjects. The Results also find more TNF protein in cultures from diabetic than nondiabetic subjects, but those groups did not differ in BMI. Thus, the paper does not establish that both mRNA and protein levels are elevated specifically in human obesity. (LLM, conf=0.86)
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Self-citation
- Authors
- Saghizadeh, M., Ong, J. M., Garvey, W. T., Henry, R. R., & Kern, P. A.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Medical University of South Carolina (US)
- University of California San Diego (US)
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Kern, P A
- Venue
- Journal of Clinical Investigation
- Published
- 1996-02-15
- Volume
- 97
- Issue
- 4
- Pages
- 1111-1116
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507159
- OpenAlex
- W2164641915
- Cited by
- 717
- References
- 25
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 11 · 2023: 11 · 2022: 9 · 2021: 15 · 2020: 22 · 2019: 19 · 2018: 30 · 2017: 15 · 2016: 24 · 2015: 23 · 2014: 24 · 2013: 31 · 2012: 19
- FWCI
- 21.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- Cedars-Sinai Medical Center
- National Institutes of Health
- School of Medicine, Indiana University
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39176, DK-38765)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- TNF-α, insulin resistance, skeletal muscle, glucose uptake, type 2 diabetes, muscle biopsy, myotubes, glucose disposal, insulin sensitivity, adipose tissue
- MeSH terms
- Adult, Animals, Base Sequence, Cells, Cultured, Diabetes Mellitus, Humans, Insulin Resistance, Molecular Sequence Data, Muscles, Obesity, RNA, Messenger, Tumor Necrosis Factor-alpha, Gene Expression, DNA Primers, Rats
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