Insulin resistance, acanthosis nigricans, and polycystic ovaries associated with a circulating inhibitor of postbinding insulin action.
A 21-yr-old moderately obese woman with hirsutism, acanthosis nigricans, and oligomenorrhoea was diagnosed as having polycystic ovary syndrome. Despite hyperinsulinemia, binding of insulin to her red cells was within the range for normal, young adult subjects. Her serum did not bind or degrade [125I]insulin or alter its binding to fat cells, and was negative for insulin receptor antibodies. However, her serum caused a dose-dependent inhibition of insulin-stimulated lipogenesis (conversion of [3-3H]glucose to [3H]lipid) in rat fat cells significantly greater than that produced with control serum (relative potency, 3.5:1) and (at a 1:20 dilution) markedly impaired the response of both lipogenesis and 2-deoxy-D-glucose uptake to maximum concentrations of insulin. After the patient was treated with clomiphene for 4 months, her menses resumed, hair growth slowed, fasting blood glucose and plasma insulin concentrations decreased, and serum inhibitory activity decreased to the control range. Serum inhibitory activity was stable to freezing and thawing and to heating at 56 C for 30 min, and could be extracted into acid-ethanol. By dialysis, its mol wt was below 1000, whereas by ultracentrifugation, it was above 3500; both high and low mol wt forms were detected after Sephadex G-50 gel chromatography of serum, suggesting that the inhibitor was of low mol wt but loosely bound to a higher mol wt component in serum. These findings indicate that insulin resistance in this patient with acanthosis nigricans and polycystic ovaries could be attributed to a circulating low mol wt inhibitor of postbinding insulin action.
D000052:Acanthosis Nigricans / Q000097:blood* / Q000150:complications; D000328:Adult; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000502:physiology; D007329:Insulin Antagonists / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis; D009765:Obesity / Q000097:blood / Q000150:complications; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications; D011972:Receptor, Insulin / Q000378:metabolism
D007328:Insulin; D007329:Insulin Antagonists; D008055:Lipids; D011972:Receptor, Insulin; D005947:Glucose