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

Abstract

We studied a patient with systemic lupus erythematosus and type B insulin resistance who showed almost complete normalization of postprandial plasma glucose 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 clinical relevance of the biological ability of anti-insulin receptor antibodies (anti-IRAb), we made multiple preparations of the patient's dialyzed serum and IgG. Dialyzed serum prepared on day 1 showed 95% inhibition of insulin binding. The binding inhibition was, however, decreased parallel to the normalization of insulin sensitivity. For 2DG uptake, 6.2 microM IgG purified 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-fold, respectively. Phosphotyrosine immunoblotting revealed that apparent insulin 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 dialyzed 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 observed in vivo. Other pathogenic factors or mechanisms in addition to the insulin-like action of the anti-IRAb may be also required to fully understand the development of fasting hypoglycemia in type B insulin resistance.

• Authors: H Yamasaki, Y Yamaguchi, N Fujita, C Kato, H Kuwahara, M D Yamauchi, K Yamakawa, T Abe, M Ozaki, Y Sera, S Uotani, E Kawasaki, H Takino, K Eguchi
• Journal: Acta diabetologica (Acta Diabetol) Vol. 37 Issue 4 Pg. 189-96 ( 2000) ISSN: 0940-5429 [Print] Germany
• PMID: 11450502 (Publication Type: Case Reports, Journal Article)

Chemical References

• Autoantibodies
• Blood Glucose
• Immunoglobulin G
• Insulin
• Recombinant Proteins
• Deoxyglucose
• Receptor, Insulin

Topics

• Animals
• Autoantibodies (blood, pharmacology)
• Biological Transport
• Blood Glucose (metabolism)
• CHO Cells
• Cricetinae
• Deoxyglucose (metabolism)
• Fasting
• Female
• Humans
• Hypoglycemia (immunology, physiopathology)
• Immunoglobulin G (blood, pharmacology)
• Infusions, Intravenous
• Insulin (administration & dosage, pharmacology)
• Insulin Resistance (immunology, physiology)
• Middle Aged
• Phosphorylation
• Postprandial Period
• Receptor, Insulin (immunology, physiology)
• Recombinant Proteins (metabolism)
• Transfection