The effect of insulin antibodies on glucose uptake by the isolated rat diaphragm

During insulin therapy generalized allergic re- actions are sometimes observed in diabetic subjects and disappear in many cases when the insulin pre- paration is changed (see Joslin, Root, White & Marble, 1952).These allergic manifestations are often the result of sensitization to impurities in the insulin preparations (Jorpes, 1949).It is also known, however, that insulin itself is antigenic and that antibodies appear in the plasma of human subjects (Berson, Yalow, Bauman, Rothschild & Newerly, 1956) and of animals (Moloney & Coval, 1955) after only short courses of insulin therapy; no such antibodies are demonstrable in human or animal subjects who have not received parenteral insulin therapy.Serum from insulin-treated human subjects and animals (i) neutralizes the convulsive effect of insulin in mice (Banting, Franks & Cairns, 1938; Lowell, 1942; Sehon, Kaye, McGarry & Rose, 1955; Moloney & Coval, 1955); (ii) binds added 131I-labelled insulin in the y-globulin (Burrows, Peters & Lowell, 1957) or between the ,B-and y- globulin (Berson & Yalow, 1957) fractions of the plasma proteins; (iii) agglutinates or haemolyses red cells conjugated with insulin (Arquilla & Stavitsky, 1956a).In the present investigations serum from guinea pigs sensitized to purified bovine insulin by the method described by Moloney & Coval (1955) was examined to determine its ability to inhibit the effects of insulin and other hypoglycaemic agents upon the isolated rat diaphragm.