Antibodies to Insulin-Like Growth Factor I Receptors in Diabetes and Other Disorders

Abstract

A newly developed immunoprecipitation assay, with 125I-labeled highly purified human placental insulin-like growth factor I (IGF-I) receptor, was used to search for IGF-I-receptor antibodies in human sera. Eleven of 141 patient sera tested (7.8%) immunoprecipitated labeled IGF-I receptor. Immunoprecipitation was comparable with sera and IgG prepared from these sera. Seven of the 11 sera (3 of 31 with rheumatic disorders, 3 of 48 with non-insulin-dependent diabetes, and 1 of 52 with insulin-dependent diabetes) failed to inhibit IGF-I binding to human placental membranes and thus contained non-binding-inhibitory IGF-I-receptor antibodies. Their pathophysiological function remained uncertain. The remaining 4 sera (2 of 3 with type B severe insulin resistance, 1 of 7 with polycystic ovary syndrome (PCO), and 1 of 31 with rheumatic disorders) inhibited IGF-I binding. Plasma IGF-I concentrations were elevated (663 and 802 ng/ml, respectively) in 2 patients (1 with PCO and another with systemic lupus erythematosus) with binding-inhibitory IGF-I-receptor antibodies, suggesting IGF-I resistance that was probably mediated by the IGF-I-receptor antibodies. In conclusion, we identified two species of human IGF-I-receptor antibodies. Sera from 7 of 141 patients tested contained IgG autoantibodies that bound to the IGF-I receptor at a locus different from the IGF-I binding site and did not inhibit IGF-I binding. Sera from 4 of 141 patients contained antibodies that bound to the IGF-I receptor at or near the IGF-I binding site, inhibited IGF-I binding, and probably caused IGF-I resistance.

Cardiomyoblast apoptosis induced by insulin-like growth factor (IGF)-I resistance is IGF-II dependent and synergistically enhanced by angiotensin II

“…Our findings may raise a further question about whether myocardial cell death in patients with hypertension induced by Ang II and impaired IGF-I system is caused by an upregulation of IGF-II system and calcineurin activity. In diabetes, IGF-I receptor antibodies bind to the IGF-I receptor at or near the IGF-I binding sites, inhibit IGF-I binding, and probably cause IGF-I resistance [6]. Besides, the circulating IGF-I levels and IGF-I function fall progressively with aging [28].…”

“…One pathway of angiotensin II induced hypertrophy and apoptosis may be calcium-calcineurin [4]. Besides, patients with diabetes mellitus often exhibit abnormalities in insulin-like growth factor (IGF)-I, such as reduced circulating levels of IGF-I [5] and increased IGF-I resistance [6]. IGF-I has been found to improve myocardial function, promote cardiac growth, improve cardiac contractility, evoke ventricular remodeling, and prevent heart failure [7].…”

Low Prevalence of Autoantibodies to the Insulin-like Growth Factor I Receptor in Children with Short Stature

“…(19) re~orted that sera from five of seven ~atients with severe ins;linmresistance and acanthosis nigricans i&unoprecip-itated both placental insulin and IGF-I receptors. Autoantibodies to the IGF-I receptor were also found in &ra from 1 1 patients with a variety of disorders reported to have an increased prevalence of insulin receptor antibodies (7). In this study, two sera from patients with severe insulin resistance type B were found to immunoprecipitate the labeled IGF-I receptor and to inhibit IGF-I binding.…”

Protective effect of Danggui (Radix Angelicae Sinensis) on angiotensin II-induced apoptosis in H9c2 cardiomyoblast cells

“…Patients with diabetes often show reduced circulating levels of IGF-I and thus develop IGF-I resistance [ 7 , 8 ]. This situation may induce apoptosis of myocardial cells and increase the risk of a heart attack.…”