Mice immunized to insulin develop antibody to the insulin receptor.

We immunized mice with insulin and found that those strains that develop insulin antibodies subsequently produce insulin-like activity in amount equivalent to 300-400 ng insulin per ml serum. The activity was due exclusively to IgG2 antibodies. Bioactivity could be blocked efficiently by insulin antibodies from guinea pigs and from mice. The active IgG2 also displaced labeled insulin from fat cells. Preliminary in vivo studies have indicated that the appearance of insulin-like antibodies in the mouse resulted in abnormal glucose homeostasis and "down regulation" of insulin receptors. These results indicate that immunization to insulin can initiate an idiotype-anti-idiotype network resulting in antibodies to the hormone receptor.