Opioid blockade effect on insulin beta-cells secretory patterns in polycystic ovary syndrome. Oral glucose load versus intravenous glucagon bolus.
In order to evaluate the involvement of endogenous opiates in the insulin disorders of polycystic ovary syndrome (PCOs) a total of 25 PCOs women and 11 normo-ovulatory controls were studied by comparing the effect of a chronic opioid blockade on beta-cells responsiveness to oral glucose load and to intravenous glucagon bolus. Each patient, studied on follicular phase, underwent to oral glucose tolerance test (OGTT), and, 2 days later, to a glucagon intravenous bolus (1 mg); these tests were then repeated after 6 weeks of naltrexone treatment (50 mg orally). Naltrexone treatment did not modify the insulin secretory patterns of control subjects, whereas the same therapy significantly reduced, in hyperinsulinemic PCOs women, the beta-cell hyperresponsiveness both to oral glucose load and to intravenous glucagon (p < 0.05 and p < 0.01, respectively), even if with different mean percent decrease (32% OGTT vs. 45% glucagon, p < 0.05). Moreover, normoinsulinemic PCOs patients showed a slight, but not significantly increase in the beta-cells response to OGTT after opioid blockade, whereas, in the same situation, the insulin release after glucagon bolus was significantly reduced (p < 0.01). Chronic opioid blockade did not modify gonadotropins, steroids and SHBG levels in either group. Our data show that naltrexone treatment is able to reduce the beta-cell response to a direct intravenous secretagogue stimulus in all PCOs patients, while only in hyperinsulinemic PCOs subjects the same treatment is effective in reducing the exaggerated insulin secretion after oral glucose load. The reason for such a discrepancy could be ascribed to a different effect of opioids on first- and second-phase insulin secretion, or, alternatively, to an involvement of other secretagogue factors, such as glucoincretins.
Ciampelli
M
M
Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy.
Fulghesu
A M
AM
Guido
M
M
Murgia
F
F
Muzj
G
G
Belosi
C
C
Fortini
A
A
Cento
R
R
Lanzone
A
A
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D005260:Female; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*
D007328:Insulin; D009292:Narcotic Antagonists; D005934:Glucagon; D005947:Glucose