INCREASED ABUNDANCE OF INSULIN INSULIN-LIKE GROWTH-FACTOR-I HYBRID RECEPTORS IN SKELETAL-MUSCLE OF OBESE SUBJECTS IS CORRELATED WITH IN-VIVO INSULIN SENSITIVITY/

We reported that in noninsulin-dependent diabetes melitus (NIDDM) pati ents expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a d efect associated with NIDDM or represents a generalized abnormality as sociated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in musc le of eight normal and eight obese subjects. Maximal insulin binding t o insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negati vely correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls ( B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and wa s negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003 ). Hybrid receptor abundance was higher in obese than in normal subjec ts (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) a nd was negatively correlated with insulin binding (r = -0.60; P < 0.01 ) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0 .70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured b y ITT (r = -0.67; P < 0.016). These results indicate that downregulati on of insulin receptors or upregulation of type 1 IGF receptors becaus e of changes in plasma insulin and IGF-I levels may result in modifica tions in hybrid receptor abundance.