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Articles in PresS, published online ahead of print May 28, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00081.2002
Submitted on February 26, 2002
Accepted on May 24, 2002
1 Pediatrics, United States Department of Agriculture/ Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: tdavis{at}bcm.tmc.edu.
Studies have shown that protein synthesis in skeletal muscle of neonatal pigs is uniquely sensitive to a physiological rise in both insulin and amino acids. Protein synthesis in cardiac muscle, skin, and spleen is responsive to insulin but not amino acid stimulation, while in the liver, protein synthesis responds to amino acids but not insulin. To determine the response of protein synthesis to insulin-like growth factor I (IGF-I) in this model, overnight-fasted 7- and 26-day-old pigs were infused with IGF-I (0, 20, or 50 µg* kg-1 * hr-1) to achieve levels within the physiological range, while amino acids and glucose were clamped at fasting levels. Because IGF-I infusion lowers circulating insulin levels, an additional group of high-dose IGF-I-infused pigs was also provided replacement insulin (10 ng * kg-0.66 * min-1). Tissue protein synthesis was measured using a flooding dose of L-[4-3H]phenylalanine. In 7-day-old pigs, low-dose IGF-I increased protein synthesis by 25 to 60% in various skeletal muscles as well as in cardiac muscle (+38%), skin (+24%), and spleen (+32%). The higher dose of IGF-I elicited no further increase in protein synthesis above that found with the low IGF-I dose. Insulin replacement did not alter the response of protein synthesis to IGF-I in any tissue. The IGF-I-induced increases in tissue protein synthesis decreased with development. IGF-I infusion, with or without insulin replacement, had no effect on protein synthesis in liver, jejunum, pancreas, or kidney. Thus, the magnitude, tissue specificity, and developmental change in the response of protein synthesis to acute, physiological increases in plasma IGF-I are similar to those previously observed for insulin. This study provides in vivo data which indicate that circulating IGF-I and insulin act on the same signaling components to stimulate protein synthesis, and that this response is highly sensitive to stimulation in skeletal muscle of the neonate.
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