Prolonged disappearance rate of a structurally abnormal mutant insulin from the circulation in humans.

The first mutant insulin, [LeuB25]insulin, was semisynthesized, and its disappearance rate from the circulation was measured. Three micrograms of normal human or [LeuB25] insulin per kg were administered to three normal subjects. The half-lives of normal insulin and the mutant insulin were 4.5 and 24 min, respectively. The decrement in blood glucose levels after injection of mutant insulin was 22.6% that after injection of normal insulin. The blood glucose-lowering effect of the mutant insulin, evaluated by the time required to reach the nadir, was slightly prolonged (30 vs. 45 min). These results indicate that hyperinsulinemia in patients with abnormal insulin is due to prolonged disappearance because of decreased receptor binding.