MOLECULAR-BASIS OF INSULIN RESISTANCE

The recent application of recombinant DNA technology to clinical inves tigation now allows the identification of the molecular alterations re sponsible for insulin resistance. In this review, the recent knowledge concerning these investigations is reported. Genetic mutations of the insulin gene as the source of insulin resistance have been reported f or a long time. More recently a series of mutations of the insulin rec eptor gene have been identified as the cause of the extreme insulin re sistance, observed in rare syndromes, such as type A insulin resistanc e or leprechaunism. However, it is probable that the majority of the m olecular defects causing insulin resistance occur at the postreceptor level. The key proteins involved in the different intracellular signal ling pathways of insulin are only partly identified. A better understa nding of the mechanisms of insulin action is essential for the identif ication of corresponding genetic alterations. The investigations conce rning the glucose transporter GLUT4 and glucokinase genes are good exa mples of complex but promising research, which has recently started. E lucidation of the genetic and molecular basis of diseases such as type Il diabetes or other states associated with insulin resistance, is th e long-term goal.