Insulin Stimulation of Aminoisobutyric Acid Transport in Human Skin Fibroblasts Is Mediated Through Both Insulin and Type I Insulin-Like Growth Factor Receptors*

Abstract

A monoclonal antibody to the human type I insulin-like growth factor (IGF-I) receptor (αIR-3) was used to distinguish actions of insulin and IGF-I that are mediated through insulin as opposed to IGF-I receptors on human skin fibroblasts. Both insulin and IGF-I stimulate uptake of the nonmetabolized alanine analog a-aminoisobutyric acid (AIB) in these cells. αIR-3 inhibited AIB uptake stimulated by both of these hormones in a dose-dependent manner. However, the pattern of hormone action in the presence of αIR-3 differed for the two hormones. In the case of IGF-I, αIR-3 potently inhibited AIB uptake at low hormone concentrations, but this inhibition was overcome by high hormone concentrations, consistent with impairment of IGF-I action through the IGF-I receptor. In the case of insulin, the action of low concentrations (i.e. 10 ng/ml) was not inhibited, but that of higher insulin concentrations was, suggesting a dual receptor mechanism of cell stimulation by insulin. αIR-3 will be an important tool in further studies of the biology of the IGF-I receptor in normal and abnormal human cells.