INSULIN-RECEPTOR NUMBER AND BINDING-AFFINITY IN NEWBORN DOGS

The insulin resistance in newborn mammals may be caused by a receptor or postreceptor defect. Although liver and umbilical cord blood monocytes have increased numbers of insulin receptors, there is a paucity of information about other neonatal tissues. Glucose disposal takes place primarily in the skeletal muscle; therefore, it is important to evaluate this tissue for an insulin receptor defect. To determine the role of insulin receptors in neonatal insulin resistance, neonatal and adult canine skeletal muscle, heart, and liver were compared for numbers of insulin receptors and their affinity for insulin. Partially purified receptors from four animals in each group were obtained by wheat germ lectin affinity chromatography and used in competition binding studies. Specific binding (mean +/- SE) in the absence of cold insulin was increased in newborn skeletal muscle (9.7 +/- 0.8 versus 4.8 +/- 0.5%, p < 0.001) and heart (8.1 +/- 1.2 versus 5.5 +/- 0.6%, p < 0.05). High-affinity insulin receptor number (mean +/- SEM) was increased in newborn skeletal muscle (183 +/- 40 versus 120 +/- 29 pM, p < 0.002) and heart (264 +/- 94 versus 157 +/- 51 pM, p < 0.05) as estimated from the X intercept of the Scatchard plot. Using half-maximal binding to estimate affinity, there were no differences between adults and newborns among all tissues studied. High-affinity receptor number and percentage of specific binding were similar for newborn and adult liver tissue. No binding defect was found, as depicted by the observations that the affinity was the same and the number of insulin receptors was the same or increased in the tissues of the newborn compared to the adult dogs. These results provide evidence that newborn insulin resistance may be caused by a postbinding defect.