Involvement of Ovarian Steroids in the Opioid-Mediated Reduction of Insulin Secretion in Hyperinsulinemic Patients with Polycystic Ovary Syndrome

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol. Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization. Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.

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Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response

Reproductive Medicine and Biology ◽

10.1007/s12522-015-0204-x ◽

2015 ◽

Vol 14 (3) ◽

pp. 123-129 ◽

Cited By ~ 1

Author(s):

Hiroaki Negishi ◽

Kazuki Nakao ◽

Michiko Kimura ◽

Hiroshi Takenaka ◽

Michiharu Horikawa

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Polycystic Ovary Syndrome ◽

Glucose Tolerance ◽

Polycystic Ovary ◽

Insulin Response ◽

Japanese Women ◽

Ovary Syndrome

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Differential insulin response to oral glucose tolerance test (OGTT) in overweight/obese polycystic ovary syndrome patients undergoing to myo-inositol (MYO), alpha lipoic acid (ALA), or combination of both

Gynecological Endocrinology ◽

10.1080/09513590.2019.1640200 ◽

2019 ◽

Vol 35 (12) ◽

pp. 1088-1093 ◽

Cited By ~ 11

Author(s):

Alessandro D. Genazzani ◽

Alessia Prati ◽

Federico Marchini ◽

Tabatha Petrillo ◽

Antonella Napolitano ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Polycystic Ovary ◽

Insulin Response ◽

Tolerance Test ◽

Oral Glucose ◽

Alpha Lipoic Acid ◽

Oral Glucose Tolerance ◽

Ovary Syndrome

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Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.0.1360410 ◽

1997 ◽

Vol 136 (4) ◽

pp. 410-415 ◽

Cited By ~ 12

Author(s):

Yilmaz Şahin ◽

Demet Ayata ◽

Fahrettin Keleştimur

Keyword(s):

Polycystic Ovary Syndrome ◽

Gnrh Agonist ◽

Polycystic Ovary ◽

Insulin Response ◽

Prospective Clinical Study ◽

Oral Glucose ◽

Fasting Insulin ◽

Ovary Syndrome ◽

C Peptide ◽

17 Hydroxyprogesterone

Abstract Objective: To determine whether hyperinsulinism affects cytochrome P450c 17α activity by investigating the correlation between 17–hydroxyprogesterone (17–OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). Design: Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17–OHP response to buserelin testing and the insulin response to oral glucose in PCOS. Methods: Twenty-eight women with PCOS and eighteen normal women were included in the study. 17–OHP response to buserelin, and insulin and C–peptide responses to oral glucose were measured. Results: Twenty–live women with PCOS had an increased 17–OHP response. The PCOS patients showed significantly higher mean post–glucose load insulin and C–peptide levels than controls (P<0·05). No significant correlations were found between basal 17–OHP and fasting insulin or fasting C–peptide, between peak 17–OHP and fasting insulin, peak insulin or peak C–peptide, between 17–OHP area under the curve (AUC) and insulin AUC or C–peptide AUC, and between percent increment in 17–OHP and insulin AUC or C–peptide AUC (P >0·05). Conclusions: Lack of a relationship between the 17–OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17α enzyme seen in PCOS. European Journal of Endocrinology 136 410–415

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Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome

Gynecological Endocrinology ◽

10.1080/09513590802342858 ◽

2008 ◽

Vol 24 (11) ◽

pp. 637-643 ◽

Cited By ~ 18

Author(s):

Bindu Kulshreshtha ◽

Mohammed Ashraf Ganie ◽

Edavan Pulikkanath Praveen ◽

Nandita Gupta ◽

Madan Lal Khurana ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Young Women ◽

Polycystic Ovary ◽

Insulin Response ◽

Oral Glucose ◽

Ovary Syndrome

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SLC6A4 5HTTLPR Polymorphism Affects Insulin Secretion in Patients with Polycystic Ovary Syndrome

International Journal of Endocrinology ◽

10.1155/2018/6130487 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Barbara Šenk ◽

Katja Goričar ◽

Nika Aleksandra Kravos ◽

Mojca Jensterle Sever ◽

Andrej Janež ◽

...

Keyword(s):

Insulin Secretion ◽

Blood Glucose ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Control Group ◽

Blood Levels ◽

Oral Glucose ◽

Ovary Syndrome ◽

Serotonin System ◽

Glucose Stimulated Insulin Secretion

Purpose. To investigate in a pilot study of genetic polymorphisms in serotonin system influencing basal- and glucose-stimulated insulin secretion in women with polycystic ovary syndrome (PCOS). Methods. A cross-sectional study included 65 female patients with PCOS followed up at the endocrine outpatient clinic of the University Medical Center Ljubljana and a control group of 94 young healthy female blood donors. Oral glucose tolerance test was performed only in PCOS patients and basal- and glucose-stimulated blood glucose and insulin levels were measured. All the subjects were genotyped for 5HTR1A rs6295, 5HTR1B rs13212041, and SLC6A4 5HTTLPR polymorphisms in the serotonin system. Results. Genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for 5HTR1A rs6295 in healthy controls and 5HTR1B rs13212041 in PCOS patients that were not consistent with HWE. SLC6A4 5HTTLPR polymorphism was significantly associated with insulin secretion (p=0.030) and with the area under the curve of insulin blood levels during OGTT (p=0.021). None of the investigated polymorphisms was significantly associated with basal- or glucose-stimulated blood glucose levels at any point in time during OGTT or with the basal insulin concentration. Conclusions. Serotonin system may play a role in glucose-stimulated insulin secretion in patients with insulin resistance (IR) and decreased insulin sensitivity. Further studies are needed to conclude whether the observed effect is characteristic for PCOS-related metabolic disturbances or for the identified mutation in different high metabolic risk populations.

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