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.
Giannini
S
S
Department of Molecular Genetics, Beckman Research Institute of the City of Hope, Duarte, California 91010.
Mohan
S
S
Kasuya
J
J
Galli
G
G
Rotella
C M
CM
LeBon
T R
TR
Fujita-Yamaguichi
Y
Y
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins