Hypoglycemia Due to Apparent Autoantibodies to Insulin: Characterization of Insulin-binding Protein

Abstract

A fifty-two year old female, admitted when unconscious, had a blood glucose level of 33 mg./100 ml. Glucose injection restored consciousness, and oral glucose loading revealed a diabetic curve. Hypoglycemic coma was not produced by tolbutamide. Total immunoreactive insulin extracted from fasting plasma ranged from 824 to 1,400 μU. per milliliter. Laparotomy did not reveal adenoma of the pancreas. The specimen of the pancreas contained 3.8 U. of insulin per gram and histologically showed an increase in the numbers of islets. Her plasma was proved to bind 131-I-insulin by gel filtration, paper chromatography and dextran-coated charcoal methods. The binding protein was identified to be gamma globulin upon paper electrophoresis and was absorbed by anti–human globulin rabbit serum. The gamma globulin was characterized as IgG on immunoelectrophoresis with radioautography. Protein fractions from the patient's plasma, freed from insulin by gel filtration after acidification, reacted with pork, beef or human insulin, and dose response curves were depicted. With bonito insulin, however, it did not show any immunologic reaction. A positive skin anaphylaxis reaction was demonstrated in a guinea pig immunized with the patient's plasma, but no precipitation reaction was observed. Since the patient had never received insulin injections, the results suggest that the insulin-binding protein contains antibodies which are produced against endogenous insulin.