TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study with no human or in vivo data.
PubMed 10329978 · doi:10.1152/ajpendo.1999.276.5.E849
What was done
Cultured C2C12 mouse myotubes were treated with tumor necrosis factor-alpha (TNF-alpha) to evaluate cellular insulin responsiveness. The investigators measured insulin receptor substrate (IRS)-1- and IRS-2-mediated phosphatidylinositol 3-kinase (PI 3-kinase) activation, IRS-1-PI 3-kinase binding, IRS-1 tyrosine phosphorylation, p42/p44 mitogen-activated protein kinase (MAPK) phosphorylation, and insulin-stimulated 2-deoxyglucose (2-DG) uptake.
What was found
TNF-alpha significantly suppressed insulin signaling and glucose uptake in C2C12 cells: - Impaired insulin stimulation of IRS-1- and IRS-2-mediated PI 3-kinase activation by 54% and 55%, respectively (P < 0.05). - Decreased insulin-stimulated IRS-1 tyrosine phosphorylation by 40% (P < 0.05). - Reduced insulin-induced p42(MAPK) and p44(MAPK) tyrosine phosphorylation by 81% (P < 0.01). - Decreased insulin-stimulated 2-DG uptake from 60 +/- 4 to 44 +/- 6 pmol.min-1.mg-1 (P < 0.05).
Why it matters
It demonstrates a direct cellular mechanism by which inflammatory cytokines like TNF-alpha, released during acute stress or tissue damage, can disrupt proximal insulin signaling cascades and blunt glucose uptake in skeletal muscle.
Limits
The study was conducted entirely in vitro using an immortalized murine cell line (C2C12), limiting direct translation to human in vivo physiology. The abstract does not report the number of experimental replicates, cytokine concentration, or exposure duration.
Cited by
- supports Elevated inflammatory cytokines cause rapid insulin resistance in humans, rodents, and cell cultures.