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


METHODS
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.


METHODS
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).


METHODS
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.
De Marinis
L
L
Institute of Endocrinology, Chair of Internal Medicine II, Catholic University School of Medicine, Rome, Italy.
Mancini
A
A
Valle
D
D
Bianchi
A
A
De Luca
A M
AM
Fulghesu
A M
AM
Villa
P
P
Mancuso
S
S
Lanzone
A
A
D000328:Adult; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood / Q000187:drug effects; D005260:Female; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009765:Obesity / Q000097:blood / Q000188:drug therapy*
D002096:C-Peptide; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D009292:Narcotic Antagonists; D019382:Human Growth Hormone; D009271:Naltrexone; D007334:Insulin-Like Growth Factor I