On the other hand, it has been reported an increased PTP-1B activity in hepatic cytosolic fractions isolated from streptozotocin (STZ)-hyperglycemic rats (Meyerovitch et al., 1989), while augmented hepatic microsomal enzyme activity, content of protein, and mRNA levels have only been observed after 2 weeks of insulin treatment in these insulinopenic organisms, suggesting that elevated insulin levels are necessary to modify PTP-1B content and activity, namely hyperinsulinemia caused by insulin resistance may lead to altered PTP-1B expression and activity (Ahmad and Goldstein, 1995). This evidence concerns the gene INS and hyperinsulinism.