Insulin-Neutralising Activity of Gamma-Globulins Derived From the Serum of an Insulin-Resistant Patient

Ethanol Fractionation of Plasma and Electrophoretic Identification of Insulin-Binding Antibody

“…However, Weiger and Colwell (3) and Peters, Burrows, and Lowell (4) have since reported that, on paper electrophoresis, insulin-I'31 migrates with the y globulins in the sera of insulin-resistant patients. In view of the reports of others that insulin-neutralizing activity present in the sera of insulin-resistant patients is restricted to the y globulin fraction (5)(6)(7) and that an anti-insulin factor present in the sera of patients with diabetic acidosis is associated with the a and /8 globulins (8), further studies seemed indicated.…”

The Role of Nonprecipitating Insulin Antibodies in Diabetes1

“…It was almost inevitable that once the existence of antibodies to insulin had been suggested, the effect of these on the insulin itself would be questioned. Studies performed on the serum of insulin resistant patients provided further impetus to the concept that antibodies to insulin inhibit the action of insulin, thus necessitating the use of of higher doses than would otherwise have been the case (1,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). In some instances the methods then available could demonstrate antibodies to insulin by direct skin testing, by passive transfer, by complement fixation or by the use of collodion particles (2,3,18,19).…”

“…7. Studies of the effect of selected plasma and added insulin on the blood sugar of animals (8,9,11,12,16,27).…”

Physical Binding of Insulin by Gamma Globulins of Insulin-Resistant Subjects12

“…Serum of insulin-resistant patients has been shown to protect mice from the hypoglycemic effect of insulin (3,4), and to prevent the in vitro action of insulin on the rat diaphragm (5). The insulin-neutralizing property of such serum has been shown by electrophoretic (6,7) and salt (8) fractionation to reside in the gamma globulin fraction. The substances in the plasma, presumably antibodies, related to the capacity of insulin to produce urticaria and allied reactions are apparently distinct from the insulin-neutralizing substances, and have been shown to reside in the beta globulin fraction (6).…”