PMID- 11595645 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20220331 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 281 IP - 5 DP - 2001 Nov TI - Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs. PG - E908-15 AB - In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feeding response and its developmental decline can be reproduced by insulin infusion, suggesting that an altered responsiveness to insulin is a primary determinant of the developmental decline in the stimulation of protein synthesis by feeding. In this study, 7- and 26-day-old pigs were either fasted overnight or fed porcine milk after an overnight fast. We examined the abundance and degree of tyrosine phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and IRS-2 in skeletal muscle and, for comparison, liver. We also evaluated the association of IRS-1 and IRS-2 with phosphatidylinositol 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 abundances were similar in muscle of 7- and 26-day-old pigs. The feeding-induced phosphorylations 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 refeeding 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 similar 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 activation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with development. Further study is needed to ascertain whether the developmental decline in the feeding-induced activation of early insulin-signaling components contributes to the developmental decline in translation initiation in skeletal muscle. FAU - Suryawan, A AU - Suryawan A AD - United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. FAU - Nguyen, H V AU - Nguyen HV FAU - Bush, J A AU - Bush JA FAU - Davis, T A AU - Davis TA LA - eng GR - R01 AR044474/AR/NIAMS NIH HHS/United States GR - R01-AR-44474/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Phosphoproteins) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor, Insulin) SB - IM MH - Animals MH - Animals, Newborn/*growth & development/metabolism MH - Fasting MH - *Food MH - Insulin/*metabolism MH - Insulin Receptor Substrate Proteins MH - Intracellular Signaling Peptides and Proteins MH - Liver/growth & development/metabolism MH - Muscle, Skeletal/growth & development/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Receptor, Insulin/metabolism MH - *Signal Transduction MH - Swine/*growth & development/metabolism EDAT- 2001/10/12 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/10/12 10:00 PHST- 2001/10/12 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/10/12 10:00 [entrez] AID - 10.1152/ajpendo.2001.281.5.E908 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2001 Nov;281(5):E908-15. doi: 10.1152/ajpendo.2001.281.5.E908.