Why There Is an IRS Insulin regulates the expression of at least 100 genes (1). This

major action of the hormone is important for normal metabolism but gains added significance in view of the fact that insulin resistance is the cornerstone of genetic diseases such as noninsulin-dependent diabetes mellitus and obesity. The possibility that faulty regulation of gene expression by insulin could result in disease is now given credence by the observations reported by Li et al. (2) in this issue of The Journal. Hypertriglyceridemia (HTG) is a risk factor for coronary heart disease. Plasma triglycerides are carried mainly in VLDL and chylomicrons, both of which contain apo CIII as a major protein constituent; several studies have suggested that the overexpression of apo CIII causes some forms of HTG (3). Perhaps most convincing is the observation that overexpression of human apo CIII in transgenic mice results in HTG (4). Chen et al. (5) showed that transcription of the hepatic ap