Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs

In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feedin g response and its developmental decline can be reproduced by insulin infus ion, suggesting that an altered responsiveness to insulin is a primary dete rminant of the developmental decline in the stimulation of protein synthesi s by feeding. In this study, 7- and 26-day-old pigs were either fasted over night or fed porcine milk after an overnight fast. We examined the abundanc e and degree of tyrosine phosphorylation of the insulin receptor (IR), insu lin receptor substrate-1 (IRS-1), and IRS-2 in skeletal muscle and, for com parison, liver. We also evaluated the association of IRS-1 and IRS-2 with p hosphatidylinositol 3-kinase (PI 3-kinase). The abundance of IR protein in muscle was twofold higher at 7 than at 26 days, but IRS-1 and IRS-2 abundan ces were similar in muscle of 7- and 26-day-old pigs. The feeding-induced p hosphorylations were greater at 7 than at 26 days of age for IR (28- vs. 13 -fold), IRS-1 (14- vs. 8-fold), and IRS-2 (21- vs. 12-fold) in muscle. The associations of IRS-1 and IRS-2 with PI 3-kinase were also increased by ref eeding to a greater extent at 7 than at 26 days (9- vs. 5-fold and 6- vs. 4 -fold, respectively). In liver, the abundance of IR, IRS-1, and IRS-2 was s imilar at 7 and 26 days of age. Feeding increased the activation of IR, IRS -1, IRS-2, and PI 3-kinase in liver only twofold, and these responses were unaffected by age. Thus our findings demonstrate that the feeding-induced a ctivation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with development. Further study is needed to ascertain whether the develop mental decline in the feeding-induced activation of early insulin-signaling components contributes to the developmental decline in translation initiat ion in skeletal muscle.