GROWTH-HORMONE INDUCES RESISTANCE TO THE MITOGENIC ACTION OF INSULIN THROUGH LOCAL IGF-I - STUDIES IN NORMAL AND PYGMY T-CELL LINES

Growth hormone (GH) and insulin have both mitogenic and metabolic acti ons. The growth-promoting effects of GH in vivo are thought to be medi ated by insulin-like growth factor-I (IGF-I), whereas the metabolic ef fects of GH are thought to be either direct or mediated by factors oth er than IGF-I. In previous studies using HTLV-II-transformed T-lymphob last cell lines established from normal individuals, we have shown tha t GH preincubation induces resistance to the growth-promoting (mitogen ic) action of insulin. In this study, using T-cell lines from 3 Americ an control subjects, 1 African control subject, and 1 African Pygmy (t he latter previously shown to be resistant to the growth-promoting act ions of both IGF-I and GH), we examined the role of local IGF-I in the mediation of GH-induced resistance to the mitogenic action of insulin . In these studies, we quantified the stimulation of T-cell colony for mation in response to insulin in the presence and absence of either GH or IGF-I. We found that 1) GH or IGF-I preincubation of normal T-cell lines completely blunts mitogenic responsiveness to subsequent stimul ation with insulin (all P< 0.001 versus either no GH or no IGF-I); 2) pretreatment with a monoclonal antibody against the IGF-I receptor blo cks both GH- and IGF-I-induced resistance to the mitogenic action of i nsulin in normal T-cell lines (both P= NS versus insulin alone); and 3 ) neither GH nor IGF-l preincubation induces resistance to the growth- promoting action of insulin in the Pygmy T-cell line (P = 0.37 and P = 0.74, respectively, versus insulin alone). We conclude from these dat a that 1) GH-induced resistance to the mitogenic action of insulin is mediated by local IGF-I, and 2) the Pygmy T-cell line does not develop insulin resistance in response to GH or IGF-I treatment because of a primary variation in IGF-I receptor function.