Characterisation of insulin-like growth factor I receptor in skeletal muscles of normal and insulin resistant subjects.
The insulin-like growth factor I receptor and the activity of its associated tyrosine kinase activity were characterised in wheat germ agglutinin extracts from skeletal muscle biopsies from nine control and ten obese Type 2 (non-insulin-dependent) diabetic subjects, who had marked peripheral in vivo insulin resistance for glucose disposal and hyperinsulinaemia. In parallel studies, the concentration of the insulin receptor and its tyrosine kinase activity were examined in the biopsy extracts and compared to the findings for the insulin-like growth factor I receptor system. Specific binding sites for insulin-like growth factor I were detected. The receptor binding of insulin-like growth factor I was not changed in the obese diabetic subjects as compared to binding activity in the biopsies from the control subjects. The molecular weight of the insulin-like growth factor I receptor alpha subunit was similar in both groups (135 kDa). The insulin-like growth factor I stimulated tyrosine kinase activity was also similar for the two groups. In contrast, insulin binding activity was 30% less in the receptor extracts from the in vivo insulin resistant group when compared to the control group. Moreover, insulin-stimulated tyrosine kinase activity was reduced in the former group by 40% when the value was corrected for insulin binding. Thus, specific insulin-like growth factor I receptors are present in human skeletal muscle. These receptors are normal in insulin resistant obese Type 2 diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Livingston
N
N
Department of Medicine, University of Rochester, School of Medicine and Dentistry, NY.
Pollare
T
T
Lithell
H
H
Arner
P
P
D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D009765:Obesity; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000378:metabolism; D012016:Reference Values; D013002:Somatomedins / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases