Anti-insulin receptor autoantibodies in a patient with type B insulin resistance and fasting hypoglycemia

We studied a patient with systemic lupus erythematosus and type B insulin r esistance who showed almost complete normalization of postprandial plasma g lucose in 3 months and a transient occurrence of fasting hypoglycemia from day 35 (i.e. the 35th day of hospitalization) to day 77. To determine the c linical relevance of the biological ability of anti-insulin receptor antibo dies (anti-IRAb), we made multiple preparations of the patient's dialyzed s erum and IgG. Dialyzed serum prepared on day 1 showed 95% inhibition of ins ulin binding. The binding inhibition was, however, decreased parallel to th e normalization of insulin sensitivity. For 2DG uptake, 6.2 muM IgG purifie d on 3 different days (days 7, 35 and 78, designated IgG-NOV, -JAN, and FEB , respectively) stimulated 2DG uptake into CHO-hIR at 3.4-, 3.1-, and 1.5-f old, respectively. Phosphotyrosine immunoblotting revealed that apparent in sulin receptor autophosphorylation was visible only with IgG-NOV, not with the IgG-JAN or -FEB. Mutation of tyrosine-960 or lysine-1018 of the insulin receptor failed to transduce the IgG's stimulatory effect. IgG-NOV was not able to stimulate the autophosphorylation of the human IGF-I receptor. In the present study, the insulin binding inhibitory activities of the dialyze d sera prepared at different time points were shown to be altered parallel to insulin sensitivity in vivo. Stimulatory activities of the patient's IgG were, however, discordant for the occurrence of fasting hypoglycemia obser ved in vivo. Other pathogenic factors or mechanisms in addition to the insu lin-like action of the anti-IRAb may be also required to fully understand t he development of fasting hypoglycemia in type B insulin resistance.