Even in this early phase of insulin resistance, as well as in later phases, increases in hepatic production of lipid enzymes and proinflammatory factors appear to play important roles in causing decreases in insulin signaling to IRS-1/PI3K, aPKC and Akt in muscle, which in turn causes further worsening of glucose tolerance and insulin resistance, and thus further activation of hepatic aPKC and increases in production of hepatic lipid and proinflammatory factors. This evidence concerns the gene IRS1 and Insulin resistance.