Impaired synergism between somatomedin C/insulin-like growth factor I and dexamethasone in the growth of fibroblasts from a patient with insulin resistance.
To explore a possible mechanism for the diminished growth potential in a patient with an unusual form of insulin resistance, somatomedin C/insulin-like growth factor I (SM-C/IGF-I) and insulin stimulation of [3H]thymidine incorporation and cell replication were compared in skin fibroblasts from the patient (DF) and normal controls. There appeared to be no generalized abnormality in cellular responsiveness to growth factors. In both DF and control cells, SM-C/IGF-I (50 ng/ml), insulin (100 ng/ml), and epidermal growth factor (5 ng/ml) stimulated [3H]thymidine incorporation 5-, 2-, and 6-fold, respectively. Low concentrations of human hypopituitary serum (0.25%) enhanced the effectiveness of SM-C/IGF-I and insulin to a similar extent in both DF and control cells. On the other hand, 10% calf serum stimulated [3H]thymidine incorporation 37-fold in control cells, while DF cells were only 50% as responsive. Preincubation of control cells with dexamethasone (10(-7) M) caused a marked synergistic increase in SM-C/IGF-I stimulated [3H]thymidine incorporation (15- to 20-fold in serum-free medium; 50- to 80-fold in 0.25% human hypopituitary serum). In contrast, preexposure to dexamethasone did not augment SM-C/IGF-I stimulation of thymidine incorporation into DNA of DF cells. Furthermore, the stimulation of cell replication by SM-C/IGF-I and insulin was potentiated by dexamethasone in control but not DF cultures. These data suggest that impairment of the synergistic action of glucocorticoids with SM-C/IGF-I and insulin regulation of fibroblast growth may be involved in the pathology of this insulin-resistant growth disorder.
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D013002:Somatomedins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013936:Thymidine