DIFFERENTIAL EFFECTS OF INSULIN ON PERIPHERAL AND VISCERAL TISSUE PROTEIN SYNTHESIS IN NEONATAL PIGS

Authors: Davis, Teresa; Fiorotto, Marta; BECKETT, PHILIP - BAYLOR COLLEGE OF MEDICIN; Burrin, Douglas - Doug; REEDS, PETER - UNIVERSITY OF ILLINOIS; WRAY-CAHEN, DIANE - USDHHS/FDA/CDRH; NGUYEN, HANH - BAYLOR COLLEGE OF MEDICIN

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2001
Publication Date: 5/1/2001
Citation: Davis, T.A., Fiorotto, M.L., Beckett, P.R., Burrin, D.G., Reeds, R.J., Wray-Cahen, D., Nguyen, H.V. 2001. Differential effects of insulin on peripheral and visceral tissue protein synthesis in neonatal pigs. American Journal of Physiology: Endocrinology and Metabolism. 280(5):E770-E779.

Interpretive Summary: We know that the rate of protein deposition is faster during the neonatal, or newborn, period than at any other stage of life. Muscle tissue grows faster than other types of tissue in newborns, and eating stimulates this growth. Insulin appears to play a major role in neonatal growth because it stimulates the use of amino acids to build protein. In this study, we examined whether the stimulation of protein synthesis by insulin in the newborn pig varies with the type of muscle fiber, whether it is specific to a particular type of protein, is caused by an increase in ribosomes, and whether it occurs in other peripheral and visceral tissues. Our results show that in the neonate, insulin regulates the stimulation of protein synthesis by feeding in the myofibrillar as well as sarcoplasmic proteins of muscles of different fiber types by increasing the efficiency of the translational process. Insulin had no effect on the number of ribosomes in muscle, nor did it seem to be involved in the feeding-induced stimulation of protein synthesis in visceral tissues. In summary, our findings demonstrate that different mechanisms regulate the growth of peripheral and visceral tissue in the neonate. This gives scientists a new understanding of an important growth support process. Because piglets are used by researchers as animal models for human babies, the results may have interesting application with regard to the growth of newborn human infants.

Technical Abstract: We recently demonstrated in neonatal pigs that the stimulation of protein synthesis in muscle with feeding can be reproduced by a physiological rise in insulin alone. In the current report, we determine whether the response of protein synthesis to insulin in the neonatal pig is: a) present in muscles of different fiber types, b) proportional in myofibrillar and sarcoplasmic proteins, c) associated with increased translational efficiency and ribosome number, and d) present in other peripheral tissues and in viscera. Hyperinsulinemic-euglycemic-amino acid clamps were performed in 7- and 26-day-old pigs infused with insulin to reproduce insulin levels present in fasted, fed, refed, and super-physiological conditions, respectively. Tissue protein synthesis was measured. Insulin increased protein synthesis in gastrocnemius muscle and, to a lesser degree, masseter muscle. The degree of stimulation of protein synthesis by insulin was similar in myofibrillar and sarcoplasmic proteins. Insulin increased translational efficiency but had no effect on ribosome number in muscle. All of these insulin-induced changes in muscle protein synthesis decreased with age. Insulin also stimulated protein synthesis in cardiac muscle and skin, but did not stimulate protein synthesis in liver, intestine, spleen, pancreas, or kidney. The results suggest that insulin mediates the feeding-induced stimulation of myofibrillar and sarcoplasmic protein synthesis in muscles of different fiber types in the neonate by increasing the efficiency of translation. However, insulin is not involved in the feeding-induced stimulation of protein synthesis in visceral tissues. Thus, different mechanisms regulate the growth of peripheral and visceral tissues in the neonate.