In the context of fatty diets and/or metabolic syndrome, impaired muscle capacity to oxidize fatty acids can lead to an accumulation of fatty acid derivatives in skeletal muscle—notably, diacylglycerol or ceramide—that, via activation of novel forms of protein kinase C and subsequent downstream activation of the kinases JNK and IKKβ, results in phosphorylations of insulin-responsive substrate-1 (IRS-1) that impede insulin signaling [279,280,281,282]. The gene discussed is INS; the disease is metabolic syndrome.