Lack of insulin resistance in fibroblasts from subjects with polycystic ovary syndrome.
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 sensitivity 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%/10(6) 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.
Department of Medicine, University of California, San Diego, La Jolla 92093, USA.
T P
TP
Ciaraldi
A J
AJ
Morales
M G
MG
Hickman
R
R
Odom-Ford
S S
SS
Yen
J M
JM
Olefsky
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism*