Insulin receptor tyrosine kinase activity is reduced in monocytes from non-obese normoglycaemic insulin-resistant subjects.
Insulin sensitivity has been quantified by i.v. insulin tolerance test (0.1 U/kg of body weight) in 18 (11 male/7 female) non-obese (body mass index range 19-25 kg/m2) normoglycaemic subjects. We then compared the tyrosine kinase activity and internalization of insulin receptor in monocytes from the six most insulin-sensitive (group 1) and the six most insulin-resistant (group 3) subjects. Tyrosine kinase activity was measured on immunopurified receptors using 32P-ATP and poly-glutamic acid 4: tyrosine 1, sodium salt (poly-glu-tyr 4:1). Insulin internalization was studied by incubating cells with 1 nmol/l 125I-insulin and measuring total cell-bound and intracellular 125I-insulin by an acid dissociation procedure. Basal (in the absence of insulin) receptor kinase activity was similar in both groups. Maximal (in the presence of 100 nmol/l insulin) kinase activity was 41% lower in group 3 (13.8 +/- 3.6 fmoles 32P-ATP incorporated vs 23.3 +/- 4.0, p = 0.1). Delta increment of receptor kinase activity after insulin stimulation (calculated by subtracting basal from maximal activity) was significantly (p < 0.05) reduced in group 3 (21.3 +/- 3.8 vs 11.1 +/- 2.1) and significantly (p < 0.05) correlated to the in vivo insulin sensitivity. Both total cell-bound (0.70 +/- 0.09% of total radioactivity added vs 0.83 +/- 0.15) and intracellular (0.39 +/- 0.05 vs 0.44 +/- 0.09) 125I-insulin were similar in the two groups. These data suggest that in non-obese, normoglycaemic subjects a defective insulin receptor tyrosine kinase activity may contribute to the development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Frittitta
L
L
Cattedra di Endocrinologia e Patologia Costituzionale, Università di Catania, Italy.
Grasso
G
G
Munguira
M E
ME
Vigneri
R
R
Trischitta
V
V
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009000:Monocytes / Q000201:enzymology*; D011972:Receptor, Insulin / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin