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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #137663
Title: PROTEIN-TYROSINE-PHOSPHATASE 1B ACTIVATION IS REGULATED DEVELOPMENTALLY IN MUSCLE OF NEONATAL PIGS

Author
item SURYAWAN, AGUS - BAYLOR COLLEGE OF MED
item DAVIS, TERESA - BAYLOR COLLEGE OF MED

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2002
Publication Date: 9/11/2002
Citation: Suryawan, A., Davis, T.A. 2003. Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs. American Journal of Physiology Endocrinology and Metabolism. 284:E47-E54.

Interpretive Summary: Insulin strongly stimulates muscle protein synthesis in the neonatal pig muscle. We previously showed that the insulin signaling pathway in neonatal muscle is very highly activated in response to feeding, and that response declines markedly as the newborn grows and develops. We wanted to determine the reason for that. We were aware of the existence of a particular protein, known as protein tyrosine phosphatase (PTP), which removes the signaling or phosphorylation in the insulin receptor. We theorized that in the muscle of neonatal pigs, the PTP is not very active, and that its level of activity would be very low, because that would allow the insulin receptor to be highly activated. We tested this theory in various ways. We examined the level of PTP activity in 7-day-old pigs, and found that, as we suspected, it was very low versus that in 26-day-old pigs. We also tested a number of different factors that regulate PTP activity, and these results confirmed our theory. Our findings provide valuable information that increases scientific understanding of the mechanisms underlying muscle characteristics in young, developing animals, which ultimately may prove useful to the improvement of children's nutrition for proper muscle development and growth.

Technical Abstract: The high activity of the insulin-signaling pathway contributes to the enhanced feeding-induced stimulation of translation initiation in skeletal muscle of neonatal pigs. Protein-tyrosine-phosphatase 1B (PTP1B) is a negative regulator of 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 or 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 7- and 26-day-old pigs. PTP1B activity in skeletal muscle was lower (P < 0.05) in 7- compared with 26-day-old pigs but in liver was similar in the two age groups. PTP1B abundances were similar in muscle but lower (P < 0.05) in liver of 7-compared with 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P < 0.05) in 7- than in 26-day-old pigs. The associations of PTP1B with IR and 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.