ISSN:
1432-0428
Keywords:
Insulin receptor
;
tyrosine-kinase
;
insulin resistance
;
muscle tissue
;
adipose tissue
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary We performed i. v. insulin tolerance test in 30 non-obese (BMI〈30 male and 〈28 female) nondiabetic (by oral glucose tolerance test) subjects and subdivided them into three groups of 10 subjects each, according to their insulin sensitivity (Kitt values). Then we compared the tyrosine-kinase activity of immunopurified insulin receptors (using32P-ATP and poly-glu-tyr (4∶1) from both muscle and adipose tissue in 7 of the most insulin-sensitive and 7 of the most insulin-resistant subjects. No difference was observed between the two groups in the basal (no insulin) receptor tyrosine-kinase activity from both tissues. In contrast, tyrosine-kinase activity response to insulin was significantly higher (p〈0.05 by 2-way ANOVA test) in receptors from both tissues of insulin-sensitive subjects. In addition, a decreased tyrosine-kinase sensitivity to insulin was observed in muscle, but not adipose, tissue of insulin-resistant subjects (insulin ED50 being 0.87±0.05 nmol/l vs 2.03±0.07,p〈0.05 in insulin-sensitive and-resistant subjects). Insulin ED50 of muscle receptor tyrosine-kinase significantly (p=0.001) correlated to both Kitt values (r=−0.79) and plasma insulin values at 120 min during OGTT (r=+0.80). Insulin receptor content, as assessed by radioimmunoassay, was similar in both muscle (7.9±1.3 and 9.2±1.9 ng/mg protein) and adipose tissue (8.2±1.3 and 7.5±1.4) of insulin-sensitive and-resistant subjects. Exon 11+ isoform of insulin receptor was similarly represented in muscle speciments from six insulin-sensitive (80±8% of total receptor content) and six resistant (78±6%) subjects. In conclusion, a defective insulin stimulation of receptor tyrosine-kinase activity is present in both muscle and adipose tissue of euglycaemic non-obese insulin-resistant subjects. This defect is, therefore, an early event in the development of insulin resistance. [Diabetologia, (1995) 38: 55–61]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02369353
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