Insulin Receptors, Familial Increase In

Okamoto et al. (1986) reported a family in which 6 persons in 3 generations had exceedingly high insulin (INS; 176730) binding to their erythrocytes (3- to 4-fold increase over the normal). Scatchard analysis showed that in each patient the increased insulin binding was due to increased binding capacity with little change in affinity. The pattern of inheritance was considered to be autosomal dominant although there was no instance of male-to-male transmission. Mononuclear leukocytes and erythrocyte ghosts also had high insulin binding. In contrast, the number of ouabain-binding sites and the kinetics of sugar transport were normal. The propositus was a 68-year-old man who had been recruited for a project to determine the normal range of insulin binding to erythrocytes. He was clinically normal and had no family or past history of either diabetes or hypoglycemia. There was no evidence of reduced red cell life span or a tendency to hemolysis; specifically, reticulocyte counts were normal. The latter feature was commented on because increased insulin binding had been reported in patients with hemolytic anemia. The authors referred to this as a 'familial disorder,' but in light of the clinical abnormality, it is difficult to justify calling this a disorder rather than a normal variation. Insulin tolerance tests and the euglycemic clamp study suggested that overall in vivo insulin sensitivity was normal in the propositus. Normal insulin sensitivity in the presence of very high insulin binding may indicate some post-binding peculiarity in the cells of the propositus. Indeed, the increased number of insulin receptors may be a secondary response to a variation at the post-receptor level.