DISTRIBUTION OF INSULIN INSULIN-LIKE GROWTH-FACTOR-I HYBRID RECEPTORSIN HUMAN TISSUES/

Insulin receptors (IR) and type 1 IGF receptors (IGF-IR) have been sho wn to form insulin/IGF-I hybrid receptors in tissues expressing both m olecules. The biological function of hybrid receptors is still undefin ed. To date there is no information about the distribution of hybrid r eceptors in human tissues. We have applied two microwell-based immunoa ssays which are capable of quantitating hybrid receptors in small samp les of human tissues and cells. Results demonstrated that the proporti on of total IGF-IR assembled as hybrids varied between 40 and 60%, thu s indicating that hybrid receptors account for a large fraction of tot al IGF-I binding in human tissues. A significant fraction of total IR was assembled as hybrids in the tissues examined, varying from 37% in placenta to 45% in hepatoma, with the exception of adipose tissue wher e the fraction of insulin receptors forming hybrids was 17%. Because h ybrid receptors bind IGF-I, but not insulin, with high affinity, it is likely that in human tissues hybrid receptors may be primarily activa ted by IGF-I rather than insulin under physiological conditions. There fore, differences in hybrid receptors distribution may contribute to r egulate tissue sensitivity to insulin and IGF-I by sequestering insuli n receptor ap-heterodimer in an IGF-I responsive form. (C) 1997 Elsevi er Science Ireland Ltd.