A case of insulin resistance associated with acanthosis nigricans.

Abstract

We described here a 12-year-old male patient with the syndrome of insulin resistance and acanthosis nigricans type A. Insulin levels at fasting state and after glucose loading were 149 + 63 ,uU/ml (mean± S.D.) and over 1,000 pU/ml respectively, while the fasting level of blood glucose was 77.7+8.9 mg/ml (mean+s.D.). A marked resistance to exogenous insulin was observed. Circulating levels of insulin antagonists such as growth hormone, cortisol and glucagon were within the normal range. Proinsulin was less than 5% of the radioimmunoassayable insulin. No insulin antibody or antireceptor antibody was detected. Insulin binding to mononuclear cells was decreased to about 50% of the controls. Analysis of membrane receptors demonstrated the normal average affinity, dissociation kinetics and negative cooperativity with a decreased number of receptors. After two days fasting, plasma IRI levels decreased to 27,aU/ml, while insulin binding kinetics were not affected ; which suggests that the receptor decrease was not secondary to hyperinsulinemia. These findings indicate that the decreased number of receptors was one of the causes for insulin resistance in this patient. insulin resistance ; acanthosis nigricans ; type A ; teen-age boy

Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans

“…These abnormalities are consistent with data from several studies showing both impaired insulin-receptor autophosphorylation [25 -27] and reduced numbers of insulin receptors in subjects with AN [13,28]. Although obesity has been found in some, but not all, studies to be associated with down-regulation of insulin receptors [29] and diminished intracellular signaling [30], obesity is unlikely to be solely responsible for the insulin resistance seen in subjects with AN [28]. In fact, 4 of our 5 subjects with AN reported that AN appeared before the presence of extreme obesity, suggesting insulin resistance and hyperinsulinemia preceded the development of extreme obesity.…”

“…In fact, defects in insulin binding [21] and post-insulin receptor function [22], and genetic defects within the insulin receptor gene have been documented in patients with AN [23,24]. These abnormalities are consistent with data from several studies showing both impaired insulin-receptor autophosphorylation [25 -27] and reduced numbers of insulin receptors in subjects with AN [13,28]. Although obesity has been found in some, but not all, studies to be associated with down-regulation of insulin receptors [29] and diminished intracellular signaling [30], obesity is unlikely to be solely responsible for the insulin resistance seen in subjects with AN [28].…”