Abstract | BACKGROUND: Obese women with polycystic ovary syndrome (PCOS) manifest impaired insulin-stimulated release of a d- chiro-inositol-containing inositolphosphoglycan (DCI-IPG) insulin mediator during oral glucose tolerance testing (OGTT), which appears to be restored by the administration of metformin. This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator. The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped. METHODS: We performed a cross-sectional case-control study at the clinical research center of an academic medical center. A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women, during which DCI-IPG bioactivity was monitored. RESULTS: At baseline, PCOS women were significantly more obese, hyperinsulinemic, and insulin resistant than the controls. During the clamp studies, DCI-IPG bioactivity increased significantly over the first 45 min of the low- insulin step of the clamp in normal nonobese women (P = 0.046) and then decreased to baseline levels; DCI-IPG increased again after initiation of the high- insulin step (P = 0.029). Despite higher insulin levels during the clamp in PCOS women, DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps. CONCLUSIONS: The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women, which may contribute to the insulin resistance in these women.
|
Authors | Jean-Patrice Baillargeon, Maria J Iuorno, Teimuraz Apridonidze, John E Nestler |
Journal | Metabolic syndrome and related disorders
(Metab Syndr Relat Disord)
Vol. 8
Issue 2
Pg. 127-36
(Apr 2010)
ISSN: 1557-8518 [Electronic] United States |
PMID | 20156067
(Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Hypoglycemic Agents
- Inositol Phosphates
- Insulin
- Polysaccharides
- inositol phosphate glycan
- Inositol
- Diazoxide
|
Topics |
- Adolescent
- Adult
- Case-Control Studies
- Cross-Sectional Studies
- Diazoxide
(administration & dosage, pharmacology)
- Female
- Glucose Clamp Technique
- Humans
- Hypoglycemic Agents
(administration & dosage, pharmacology)
- Inositol
(chemistry, metabolism)
- Inositol Phosphates
(chemistry, metabolism)
- Insulin
(administration & dosage, blood, metabolism, pharmacology)
- Obesity
(blood, complications, metabolism)
- Polycystic Ovary Syndrome
(blood, complications, metabolism)
- Polysaccharides
(chemistry, metabolism)
- Signal Transduction
(drug effects)
- Young Adult
|