Lack of insulin resistance in fibroblasts from subjects with polycystic ovary syndrome☆

Abstract 

Insulin resistance in polycystic ovary syndrome (PCOS) is characterized by a novel defect in insulin signal transduction expressed in isolated human adipocytes as impaired insulin senstivity for glucose transport and antilipolysis. To determine whether this is a generalized defect of a potentially genetic basis, or possibly a tissue-specific one, fibroblast cultures were established from age- and weight-matched obese normal cycling (NC; n = 5) and PCOS (n = 6) subjects. Adipocytes from the current PCOS subjects displayed impaired sensitivity for glucose transport stimulation (half-maximal effective concentration [EC₅₀], 317 ± 58 pmol/L in PCOS v 130 ± 40 in NC; P < .025). Specific insulin binding was similar in fibroblasts from NC (0.57% ± 0.10%/10⁶ cells) and PCOS (0.45% ± 0.10%) subjects. Fibroblasts from NC (4.9- ± 0.5-fold stimulation) and PCOS (4.6- ± 0.3-fold) subjects were equally responsive to insulin for stimulation of glucose incorporation into glycogen. Insulin sensitivity for glycogen synthesis in fibroblasts did not differ between NC (EC₅₀, 9.6 ± 0.9 nmol/L) and PCOS (9.1 ± 0.9) cells. For thymidine incorporation into DNA, relative insulin responsiveness was similar in NC (2.3- ± 0.3-fold stimulation) and PCOS (2.1- ± 0.1-fold) fibroblasts. Insulin sensitivity for DNA synthesis was similar in NC (EC₅₀, 12.9 ± 2.4 nmol/L) and PCOS (7.6 ± 1.3) cells. In summary, (1) insulin receptor binding is normal in PCOS fibroblasts; and (2) PCOS fibroblasts have normal insulin sensitivity and responsiveness for metabolic and mitogenic responses. Impaired insulin signal transduction, while present in adipocytes from a group of PCOS subjects, is not found in fibroblasts from the same subjects. This defect is not generalized to all cell types, but may be limited to specific tissues and responses.

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