Simultaneous Inhibition of Insulin and Somatomedin-C Binding to Cultured IM-9 Lymphocytes by Naturally Occurring Antireceptor Antibodies

A 53-yr-old male patient with insulin-resistant diabetes was found to have circulating inhibitors of both insulin and somatomedin-C binding. Serum obtained from the patient at the time of initial presentation inhibited 50% of both ¹²⁵I-insulin and ¹²⁵I-SM-C binding to IM-9 lymphocytes at dilutions of 1:150. Spontaneous improvement in the patient's diabetic state was associated with a simultaneous and equal decrease in the serum inhibitory titers for both radioligands. Scatchard analysis indicated that the observed serum-induced decrease in both insulin and SM-C binding was due to decreased receptor affinity, with no alteration in receptor number. The serum inhibitors of both insulin and SM-C binding were precipitated equally by Staph-A and also by 40% ammonium sulfate, suggesting they were immunoglobulins. The observation of naturally occurring autoantibodies against both the insulin and SM-C receptors suggests a structural homology between the two receptors.