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 mu scle 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 resis tance, 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 patien ts with moderate obesity. IR content was significantly reduced in insulin-resistant subjects both non obese 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 conte nt was not different in insulin-sensitive us. insulin-resistant subjects (b oth 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 tha t, in insulin-resistant subjects without diabetes or severe obesity, muscle LR 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 decrea se and insulin resistance.