Research
Hormonal
Elevated circulating free fatty acids (FFAs) lead to intracellular lipid accumulation (diacylglycerol and triglycerides) in non-adipose tissues, which activates serine kinases (PKC, IKK, JNK) that phosphorylate IRS proteins, inhibiting insulin signaling and causing insulin resistance.
Managing fat intake and reducing excess calories can lower circulating FFAs, preventing lipid accumulation in muscles and liver, which helps maintain proper insulin signaling.
GoodSupportsHIGH confidence
Intracellular accumulation of DG, allosteric activator of PKCs, activates PKCs, including PKC-epsilon, gamma, and zeta, that increase serine phosphorylation of IRS proteins, leading to inhibition of insulin signaling and insulin resistance.
Why this rating
Supported by multiple studies cited in the review.
Source
Role of Mitochondrial Dysfunction in Insulin Resistance
Jeong‐a Kim et al. · Circulation Research · 2008
DOI 10.1161/circresaha.107.165472
narrative_reviewCited 1,105×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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