Document Detail

Growth hormone induces insulin resistance in Laron dwarf cells via lactogenic receptors.
MedLine Citation:
PMID:  8473379     Owner:  NLM     Status:  MEDLINE    
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 micrograms/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 micrograms/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.
M E Geffner; N Bersch; D W Golde
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  76     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1993 Apr 
Date Detail:
Created Date:  1993-05-18     Completed Date:  1993-05-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1039-47     Citation Subset:  AIM; IM    
Department of Pediatrics, University of California Medical Center, Los Angeles 90024.
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MeSH Terms
Antibodies / immunology
Cell Line, Transformed
Dwarfism / pathology,  physiopathology*
Growth Hormone / pharmacology*
Insulin Resistance*
Insulin-Like Growth Factor I / pharmacology
Prolactin / pharmacology
Receptors, Prolactin / immunology,  physiology*
Receptors, Somatotropin / immunology,  physiology*
T-Lymphocytes / drug effects*
Grant Support
Reg. No./Substance:
0/Antibodies; 0/Receptors, Prolactin; 0/Receptors, Somatotropin; 67763-96-6/Insulin-Like Growth Factor I; 9002-62-4/Prolactin; 9002-72-6/Growth Hormone

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