Impaired insulin degradation in a patient with insulin resistance and acanthosis nigricans.
The kinetics of plasma insulin were studied in a 14 year old girl with the syndrome of insulin resistance and acanthosis nigricans. The clearance of plasma insulin was found to be strikingly reduced (135 ml/min . m2 versus 456 +/- 22 in 17 normal control subjects), whereas the basal systemic insulin delivery rate was increased about 10-fold (25.5 mU/min . m2 versus 2.6 +/- 0.3 in normal subjects). Thus, reduced insulin clearance and excessive posthepatic delivery of the hormone both contributed to the severe fasting hyperinsulinemia (218 microunits/ml) associated with the other clinical features of the syndrome (glucose intolerance, primary amenorrhea, polycystic ovaries, hirsutism). Following ovarian wedge resection, insulin clearance rose to 264 ml/min . m2, and insulin delivery fell to 9.8 microunits/ml min . m2. The resulting abatement of the patient's hyperinsulinism (fasting plasma insulin = 37 microunits/ml) was accompanied by the appearance of menses, normalization of glucose tolerance, and amelioration of the acanthosis. The improvement in menstrual function and acanthosis, however, was not sustained. This case provides evidence for interdependence of insulin action and insulin degradation in humans.
D000052:Acanthosis Nigricans / Q000150:complications / Q000378:metabolism*; D000293:Adolescent; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007700:Kinetics; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism / Q000601:surgery
D007328:Insulin