EFFECT OF NALTREXONE TREATMENT ON INSULIN-SECRETION, INSULIN ACTION AND POSTPRANDIAL THERMOGENESIS IN OBESITY

For many years a series of studies has been carried out to evaluate th e role of endogenous opioid peptides on glucose metabolism. In this wo rk we studied the influence of endogenous opioid peptides on insulin r esponse to OGTT and glucose-induced thermogenesis before and after a p rolonged oral treatment with Naltrexone (50 mg/daily for 6 days), an o pioid receptor antagonist, in a group of 9 obese subjects. Moreover in obese patients we evaluated the effect of this anti-opioid drug on in sulin secretion and insulin sensitivity during an IVGTT using the mini mal model approach. We compared the pre-treatment results with data co ming from a group of 5 normal-weight subjects. We measured blood gluco se, plasma insulin and C-peptide concentrations and evaluated the foll owing parameters: first (Phi 1) and second (Phi 2) phase of beta-cell sensitivity, insulin sensitivity and glucose effectiveness. Obese subj ects displayed an increased insulin response to oral and i.v. glucose load due to an increased first phase of insulin secretion (Phi 1), a r educed insulin sensitivity (Si) and glucose effectiveness (Sg) in resp ect to normal-weight subjects. They showed no difference in glucose an d insulin area during oral load and in their profiles during i.v. gluc ose load after naltrexone treatment. Similarly no significant variatio n in insulin sensitivity and glucose effectiveness was observed. The g lucose-induced thermogenesis, measured by indirect calorimetry, was no t modified by naltrexone. Therefore our study demonstrates that endoge nous opioids do not play any role in the impairment of peripheral insu lin sensitivity and energy expenditure in human obesity.