Selective insulin resistance in the polycystic ovary syndrome

Carol Beth Book, Andrea Dunaif*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia that is amplified by insulin in the presence of resistance to insulin's action to stimulate glucose uptake in muscle and fat. To explore the mechanisms for this paradox, we examined the metabolic and mitogenic actions of insulin and insulin-like growth factor I (IGF-I) in cultured skin fibroblasts from PCOS (n = 16) and control (n = 11) women. There were no significant decreases in the number or affinity of insulin- or IGF-I-binding sites in PCOS compared to control fibroblasts. Basal rates were similar, but there ware significant decreases in insulin-stimulated (control, 51.8 ± 7.0; PCOS, 29.5 ± 2.9 nmol/106 cells·2 h at 1,000,000 pmol/L; P < 0.005) and IGF-I-stimulated (control, 48.9 ± 6.7; PCOS, 33.0 ± 3.2 PCOS nmol/106 cells·2 h at 100,000 pmol/L IGF-I; P < 0.05) glucose incorporation into glycogen in PCOS fibroblasts, a metabolic action of insulin. Stimulation of thymidine incorporation, a mitogenic action of insulin, was similar in PCOS and control fibroblasts in response to both insulin and IGF-I. There were also no significant differences in insulin- or IGF-I-stimulated insulin receptor substrate-1-associated phosphatidylinositol-3-kinase activity in PCOS compared to control fibroblast cells. We conclude that 1) there is a selective defect in insulin action in PCOS fibroblasts that affects metabolic, but not mitogenic, signaling pathways; 2) there is a similar defect in IGF-I action, suggesting that insulin and IGF-I stimulate glycogen synthesis by the same postreceptor pathways; and 3) insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activation by insulin and IGF-I is similar to the control value, suggesting that the metabolic signaling defect is in another pathway or downstream of this signaling step in PCOS fibroblasts.

Original languageEnglish (US)
Pages (from-to)3110-3116
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number9
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Selective insulin resistance in the polycystic ovary syndrome'. Together they form a unique fingerprint.

Cite this