Insulin/insulin-like growth factor I hybrid receptors overexpression is not an early defect in insulin-resistant subjects.
Hybrid receptors (HRs), insulin receptor (IR)/insulin-like growth factor I receptor (IGF-I-R) heterodimers have been reported increased in skeletal muscle of obese and type 2 diabetic patients and to contribute to the patient insulin resistance. To investigate whether or not the increased expression of hybrid receptors is an early defect (probably genetic) of insulin resistance, we measured by specific enzyme-linked immunosorbent assays both IR, IGF-I-R, and HR content in skeletal muscle of healthy nonobese, nondiabetic subjects either insulin sensitive or insulin resistant, and also in patients with moderate obesity. IR content was significantly reduced in insulin-resistant subjects both nonobese and obese, compared with insulin-sensitive subjects (2.32+/-0.26, 2.36+/-0.18, and 3.45+/-0.42 ng/mg protein, respectively, P = 0.002). In contrast, IGF-I-R content was similar in the three groups. Muscle HR content was not different in insulin-sensitive vs. insulin-resistant subjects (both nonobese and obese) (4.90+/-0.46, 4.69+/-0.29, and 4.91+/-0.25 ng/mg protein, respectively, P = not significant). These studies indicate that, in insulin-resistant subjects without diabetes or severe obesity, muscle IR content but not IGF-I-R or HR content is reduced. They do not suggest, therefore, a primary (genetic) role of increased HR as a cause of IR decrease and insulin resistance.
Spampinato
D
D
Istituto di Medicina Interna, Endocrinologia e Malattie del Metabolismo, Ospedale Garibaldi, Università di Catania, Italy.
Pandini
G
G
Iuppa
A
A
Trischitta
V
V
Vigneri
R
R
Frittitta
L
L
D000328:Adult; D000368:Aged; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D055503:Protein Multimerization; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000378:metabolism*; D011972:Receptor, Insulin / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values
D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin