Growth hormone induces insulin resistance in Laron dwarf cells via lactogenic receptors Journal Article


Authors: Geffner, M. E.; Bersch, N.; Golde, D. W.
Article Title: Growth hormone induces insulin resistance in Laron dwarf cells via lactogenic receptors
Abstract: GH is the hormone primarily responsible for regulating body size within the genetic program. While GH has pleiotropic actions on cellular growth and metabolism, most of its effects are believed to be mediated by a single GH receptor. This receptor is not functional in tissues from patients with Laron dwarfism. We used human T-cell leukemia virus-immortalized T-lymphoblast cell lines from Laron dwarfs and normal individuals to examine the mechanism of GH-induced insulin resistance at the cellular level. GH (5-500 μg/L) caused a profound decrease in the sensitivity of normal T-lymphoblasts in response to all insulin concentrations (P < 0.0001 vs. insulin alone); pretreatment with GH and GH receptor antibody significantly improved sensitivity to all concentrations of insulin (P = NS vs. insulin alone). Preincubation with GH and PRL receptor antibody was associated with partial improvement in insulin sensitivity (P = 0.004 vs. insulin alone). Thus, in normal T-cell lines, the major pathway of GH-induced insulin resistance appears to be directed by the GH receptor, with a smaller effect mediated through the PRL receptor. While T-cell lines from Laron dwarfs do not respond to GH in clonal proliferation assays, GH (50 and 100 μg/L) caused profound insulin resistance in these cells (P = 0.008 and P < 0.0001, respectively, vs. insulin alone). GH receptor antibody did not abrogate this effect at any insulin concentration (P = NS vs. insulin alone), but there was partial restoration of insulin sensitivity when GH and PRL receptor antibody were coincubated (P = 0.0069 vs. insulin alone). Thus, in Laron T-cell lines, PRL and perhaps other lactogenic receptors appear to mediate GH-induced insulin resistance. The kinetics of GH-induced insulin resistance in Laron T-cells were also distinct from the pattern seen in normal T-cells, and unlike in normal cells, GH had no effect on insulin-like growth factor-I-induced clonal expansion of Laron T-cell lines (P = NS vs. insulin-like growth factor-I alone). These results provide evidence for an alternative pathway of GH action revealed in cells lacking classical growth responses to GH. © 1993 by The Endocrine Society.
Keywords: adolescent; adult; controlled study; human cell; case report; t lymphocyte; t-lymphocytes; growth hormone; cell line, transformed; insulin resistance; human immunodeficiency virus; antibodies; insulin-like growth factor i; growth hormone receptor; receptors, somatotropin; prolactin; receptor antibody; dwarfism; human; male; priority journal; article; prolactin receptor; support, u.s. gov't, p.h.s.; t lymphoblast; receptors, prolactin
Journal Title: Journal of Clinical Endocrinology and Metabolism
Volume: 76
Issue: 4
ISSN: 0021-972X
Publisher: Oxford University Press  
Date Published: 1993-04-01
Start Page: 1039
End Page: 1047
Language: English
DOI: 10.1210/jcem.76.4.8473379
PUBMED: 8473379
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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  1. David Golde
    127 Golde