CANDIDATE GENES FOR INSULIN-RESISTANCE

Insulin resistance confers increased susceptibility to NIDDM, atherosc lerotic cardiovascular disease, ovarian hyperandrogenism, and possibly hypertension. Insulin resistance is largely inherited, in rare cases as a monogenic disorder or more commonly as a complex trait. The searc h for insulin resistance genes relies mainly on two complementary appr oaches: 1) positional cloning using random DNA markers present through out the genome; and 2) the analysis of specific candidate genes. This report briefly summarizes the candidate gene approach to insulin resis tance. Progress related to the analysis of genes encoding molecules th at participate in insulin action is reviewed. In addition, the spectru m of potential generic defects that might contribute to insulin resist ance, both at the level of the target cell and secondarily (e.g., obes ity genes), is discussed.