CHARACTERIZATION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS PRODUCED BY CULTURED FIBROBLASTS FROM PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS, INSULIN-DEPENDENT DIABETES-MELLITUS, OR OBESITY

To evaluate whether the production of insulin-like growth factor-binding proteins (IGFBPs) is altered in various pathological states due to modification of the hormonal milieu, we analyzed patterns of IGFBPs released into conditioned medium during 48-h serum-free culture of early passages of human skin fibroblasts from control subjects and patients with metabolic disorders. IGFBP-2, -3, -4, and -5 were identified in the conditioned medium by immunoblotting or RIA. Compared with those in eight control subjects by ligand blot analysis, the levels of IGFBP-3, -2, and -5 were reduced to 43%, 47%, and 53% in 10 noninsulin-dependent diabetic patients, respectively whereas the levels of IGFBP-3 and -2 were reduced to 36% and 23%, respectively, in 3 nondiabetic obese patients with impaired glucose tolerance. In 2 insulin-dependent diabetic patients, the level of IGFBP-3 was reduced by 25% and 40%, respectively, and IGFBP-2 was not detectable. In contrast, a similar level of IGFBP-4 was detected in both normal and patient's conditioned media, except in 1 insulin-dependent diabetic patient. These data indicate that fibroblasts derived from patients with metabolic disorders retain their intrinsic characteristics even after they are removed from their in vivo hormonal milieu.