Insulin receptor tyrosine-kinase activity is altered in both muscle and adipose tissue from non-obese normoglycaemic insulin-resistant subjects.
We performed i.v. insulin tolerance test in 30 non-obese (BMI < 30 male and < 28 female) non-diabetic (by oral glucose tolerance test) subjects and subdivided them into three groups of 10 subjects each, according to their insulin sensitivity (K(itt) values). Then we compared the tyrosine-kinase activity of immunopurified insulin receptors (using 32P-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 K(itt) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Grasso
G
G
Cattedra di Endocrinologia e Patologia Costituzionale, Università di Catania, Italy.
Frittitta
L
L
Anello
M
M
Russo
P
P
Sesti
G
G
Trischitta
V
V
D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D009765:Obesity; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose