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Title: DEVELOPMENTAL CHANGES IN THE FEEDING-INDUCED ACTIVATION OF THE INSULIN-SIGNALING PATHWAY IN NEONATAL PIGS

Author
item SURYAWAN, AGUS - BAYLOR COLLEGE OF MED
item NGUYEN, HANH - BAYLOR COLLEGE OF MED
item BUSH, JILL - BAYLOR COLLEGE OF MED
item Davis, Teresa

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/11/2001
Publication Date: 11/1/2001
Citation: Suryawan, A., Nguyen, H.V., Bush, J.A., Davis, T.A. 2001. Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs. American Journal of Physiology - Endocrinology and Metabolism. 281(5):E908-E915.

Interpretive Summary: Researchers would like to increase their understanding of why muscle grows faster at the newborn stage than later in life. The faster rate is due to a greater responsiveness to feeding, which stimulates increased protein synthesis, but the mechanism is unknown. We studied piglet models, one for the newborn and one for a later stage of growth, and we examined the response to feeding in the muscle. The newborn pig had an increased sensitivity to insulin that declined with age. The higher rate of muscle protein synthesis after birth appeared to relate to the muscles' increased sensitivity to insulin after a meal. The proteins which we measured in the muscles were more responsive to insulin after feeding. There was an increased stimulation of muscle protein synthesis after feeding in the newborn, that was related to an enhanced activation of early insulin signaling steps. That higher level of activation may lead to increased muscle protein synthesis. These valuable findings increase our understanding of what happens during the growth and appropriate development of newborn babies, and open the door to further productive research investigations involving the type of feeding (continuous or individual meals) that best encourages the growth of newborns.

Technical Abstract: 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.