Influence of chronic Naltrexone treatment on growth hormone and insulin secretion in obese subjects

Int J Obes Relat Metab Disord. 1997 Nov;21(11):1076-81. doi: 10.1038/sj.ijo.0800519.


Objective: Recent studies have demonstrated the restoration of a normal 24 h GH profile induced by a reduction of insulinaemia after weight loss, suggesting a reciprocal relationship between plasma insulin and GH concentrations. We aimed to clarify if an opiate-induced reduction in plasma insulin could affect GH secretion in obesity.

Design: We have studied the insulin response to an oral glucose tolerance test (OGTT) and the GH response to GHRH before and after prolonged treatment with Naltrexone (NTX). C-peptide, IGF-I, IGFBP-3 plasma levels and the IGF-I/IGFBP-3 molar ratio were also determined.

Subjects: Twelve obese women (aged 25-41 y; Body mass index (BMI): 31-39 kg/m2) and six lean normal women (aged 25-38; BMI: 19.8-23.1 kg/m2).

Measurement: GH was determined by the IRMA method; insulin, C-peptide, IGF-I and IGFBP-3 were assayed by the RIA method. For molar comparison between IGF-I and IGFBP-3 we have considered 30.5 kDa the molar weight of IGFBP-3. Results are expressed as mean +/- s.e.m.

Results: We observed a significant decrease in basal concentration of both insulin (230.1 +/- 34.9 vs 133.2 +/- 16.9 pmol/L; P < 0.005) and C-peptide (3.7 +/- 0.3 vs 2.4 +/- 0.1 micrograms/L; P < 0.02). No modifications in the insulin secretory response to the OGTT were observed. A significant increase of the GHRH-induced GH peak response (7.7 +/- 1.4 vs 19.7 +/- 3.1 micrograms/L; P < 0.01) and GH-AUC (533 +/- 151 vs 1415 +/- 339 micrograms/L/120 min; P < 0.01) was found after NTX treatment. A negative correlation was found between basal insulin and GH peak values, both before (r = -0.641, P = 0.027) and after NTX (r = -0.714, P = 0.013). No modifications were found in IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio. Moreover, NTX affected neither the insulin response to OGTT or IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio in a group of six lean controls. Conversely, NTX significantly reduced the GH response to GHRH, when expressed as both peak and AUC values.

Conclusions: The opiate antagonist significantly reduced basal insulin concentrations and augmented the GH response to GHRH in obese subjects. In the absence of modifications in IGF-I and IGFBP-3 plasma levels and their molar ratio, we propose that insulin may exert a negative feedback on GH secretion.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Body Mass Index
  • C-Peptide / blood
  • C-Peptide / drug effects
  • Female
  • Glucose Tolerance Test
  • Human Growth Hormone / blood*
  • Humans
  • Insulin / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / drug effects
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / therapeutic use*
  • Obesity / blood
  • Obesity / drug therapy*


  • C-Peptide
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Narcotic Antagonists
  • Human Growth Hormone
  • Naltrexone
  • Insulin-Like Growth Factor I