Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome.
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.
Baillargeon
Jean-Patrice
JP
Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Quebec, Canada. JP.Baillargeon@USherbrooke.ca
Iuorno
Maria J
MJ
Apridonidze
Teimuraz
T
Nestler
John E
JE
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007294:Inositol / Q000737:chemistry / Q000378:metabolism*; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000150:complications / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
D007004:Hypoglycemic Agents; D007295:Inositol Phosphates; D007328:Insulin; D011134:Polysaccharides; C028039:inositol phosphate glycan; D007294:Inositol; D003981:Diazoxide