E-00210-2002-R1 0 FINAL ACCEPTED VERSION Protein Tyrosine Phosphatase 1B Activation Is Developmentally Regulated in Muscle of Neonatal Pigs

The high activity of the insulin signaling pathway contributes to the enhanced feedinginduced stimulation of translation initiation in skeletal muscle of neonatal pigs. Protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of the tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1). The activity of PTP1B is determined mainly by its association with IR and Grb2. We examined the level of PTP1B activity, PTP1B protein abundance, PTP1B tyrosine phosphorylation, and the association of PTP1B with IR and Grb2 in skeletal muscle and liver of fasted and fed, 7and 26-day-old pigs. PTP1B activity in skeletal muscle was lower (P 0.05) in 7compared to 26-day-old pigs but in liver was similar in both age groups. PTP1B abundances were similar in muscle but lower (P 0.05) in liver of 7compared to 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P 0.05) in 7than in 26day-old pigs. The association of PTP1B with IR and the association of PTP1B with Grb2 were lower (P 0.05) at 7 than at 26 days of age in muscle but there were no age-effects in liver. Finally, in both age groups, fasting did not have any effect on these parameters. These results indicate that basal PTP1B activation is developmentally regulated in skeletal muscle of neonatal pigs, consistent with the developmental changes in the activation of the insulin signaling pathway reported previously. Reduced PTP1B activation in neonatal muscle likely contributes to the enhanced insulin sensitivity of skeletal muscle in neonatal pigs.