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.