Research
Hormonal
Pro-inflammatory adipokines such as TNF-α and IL-6 induce insulin resistance by activating kinases (JNK, IKKβ) that phosphorylate IRS1/2 on serine residues, thereby inhibiting tyrosine phosphorylation and downstream insulin signaling.
Insulin resistance isn't just about 'too much insulin'; it's about the signal being blocked. Inflammation from fat tissue activates specific enzymes (JNK, IKKβ) that physically block the insulin receptor's ability to work by modifying key proteins (IRS) at the wrong spot (serine instead of tyrosine).
StrongSupportsHIGH confidence
SOCS1/3 induced by inflammatory adipokines such as TNF-α, IL-6, and IL-1β enhance the degradation of IRS1/2... IRS phosphorylation on serine residues is another mechanism to induce insulin resistance... increased TNF-α and saturated free fatty acids in obese individuals activate JNK and inhibitor of nuclear factor κB kinase β (IKKβ) to phosphorylate Ser-307 of IRS.
Why this rating
Detailed molecular pathway described with specific kinase and residue references (Ser-307).
Source
Adipokines Mediate Inflammation and Insulin Resistance
Hyokjoon Kwon et al. · Frontiers in Endocrinology · 2013
DOI 10.3389/fendo.2013.00071
narrative_reviewCited 662×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Obesity-induced insulin resistance is mediated by an imbalance in pro- and anti-inflammatory adipokines, where increased pro-inflammatory adipokines (e.g., TNF-α, IL-6, leptin) and decreased anti-inflammatory adipokines (e.g., adiponectin) trigger inflammatory signaling cascades that suppress insulin receptor substrate (IRS) phosphorylation.Good
- Adipose tissue immune cell composition shifts in obesity from anti-inflammatory (M2 macrophages, Th2 T cells, Tregs) to pro-inflammatory (M1 macrophages, Th1 T cells, CD8+ T cells), driving local and systemic inflammation that contributes to insulin resistance.Good
- Adiponectin, an anti-inflammatory adipokine, improves insulin sensitivity by activating AMPK to enhance fatty acid oxidation and glucose uptake, but its levels are decreased in obesity due to suppression by inflammatory signals.Good
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