Hyperglycemia contributes to the accumulation of toxic lipid metabolites leading to protein kinase-C activation (PKC-ε isoform, with no changes observed for PKC-α, PKC-δ, and PKC-θ isoforms) and inhibition of insulin signaling, glucose transport, and insulin-mediated vasodilation, supporting the concept of glucolipotoxicity (174, 175). The gene discussed is INS; the disease is Hyperglycemia.