Ovarian insulin resistance and insulin sensitizer effect on polycystic ovary syndrome
- VernacularTitle:胰岛素增敏剂对多囊卵巢综合征患者卵巢局部胰岛素抵抗的影响
- Author:
Xiaoke WU
;
Risto ERKKOLA
;
- Publication Type:Journal Article
- Keywords:
Polycystic ovary syndrome;
Thiazoles;
Insulin resistane
- From:
Chinese Journal of Obstetrics and Gynecology
2000;0(12):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the molecular defects of insulin signalling in polycystic ovary and in vitro effects of troglitazone, one of the insulin sensitizers thiazolidinediones on polycystic ovary syndrome(PCOS) Method The metabolic and mitogenic effects of insulin and insulin like growth factor 1 (IGF 1) were examined in cultured human ovarian luteinizing granulosa cells from PCOS ( n = 11) and normally ovulatory (as control, n = 33) women with vehicle or troglitazone (1 ?g/ml) Results Basal rates were similar, but there were significant decreases in insulin stimulated glucose incorporation into glycogen in PCOS cells, a metabolic action of insulin However, IGF 1 response was found to be about twice greater in PCOS cells at all experimental concentrations with respect to thymidine incorporation compared to control cells, a mitogenic action Troglitazone increased 2 3 fold the insulin induced glycogen synthesis, but reduced the IGF 1 augmented responses of DNA synthesis in PCOS cells to within the range of control granulosa cells As compared with control, PCOS granulosa cells had higher insulin receptor substrate 1 (IRS 1) expression, but lower IRS 2 expression IRS 2 protein levels were increased and IRS 1 levels were reduced by troglitazone treatment, with a greater extent in the former Conclusions There is a selective defect in insulin actions in PCOS granulosa cells, suggesting ovarian insulin resistance and this metabolic phenotype is associated with an enhanced IGF 1 mitogenic potential Troglitazone could divergently alter signal protein expressions and thus insulin actions, as an ovarian insulin sensitizer and mitogen/steroidogenic inhibitor in PCOS