Submitted to: Journal of Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/30/2001
Publication Date: 12/1/2001
Citation: BURRIN, D.G., STOLL, B., FAN, M.Z., DUDLEY, M.A., DONOVAN, S.M., REEDS, P.J. BIOCHEMICAL AND MOLECULAR ACTION OF NUTRIENTS ORAL IGF-I ALTERS THE POSTTRANSLATIONAL PROCESSING BUT NOT THE ACTIVITY OF LACTASE-PHLORIZIN HYDROLASE IN FORMULA-FED NEONATAL PIGS. JOURNAL OF NUTRITION. 2001. v. 131. p. 2235-2241 Interpretive Summary: Prior research has shown that piglets fed colostrum, or mother's first milk, experienced changes in the expression of lactase, which is the enzyme responsible for the digestion of lactose, the major carbohydrate in milk. In developing mammals, lactase activity normally increases to reach a peak late in gestation, presumably to prepare the newborn to digest the lactose in milk. Thus, babies born prematurely may not be as well equipped as term babies to digest their milk. A substance called Insulin-like growth factor I (IGF-I) is abundant in colostrum. Some studies with newborn pigs and rats have shown that orally administered IGF-I appears to stimulate intestinal growth and lactase activity. Since the pig is a model for the human infant, we used piglets to pursue this line of research to gain more information that might help new or premature babies with feeding intolerance and related intestinal problems. We evaluated the effects of two doses of IGF-I added to formula and fed to newborn pigs to see if their lactase activity would increase. That did not prove to be the case, although the doses did affect lactase synthesis and processing, we also found important differences in these functions in different parts of the intestine. Our results are illuminating, in that they shed light on appropriate directions for future research in this crucial study area involving infants' digestive processes.
Technical Abstract: To determine the cellular mechanism whereby oral insulin-like growth factor I (IGF-I) increases intestinal lactase-phlorizin hydrolase (LPH) activity, we studied 2-d-old pigs fed cow's milk formula (control, n=5), formula + low IGF-I (0.5 mg/L; n=6) or formula + high IGF-I (12.0 mg/L, n=6) for 15 d. On d 15, intestinal protein synthesis and lactase processing were measured in vivo in fed pigs using a 6-h intravenous, overlapping infusion of multiple stable isotopes (2H3-Leu,13C1-Leu,13C1-Phe,2H5-Phe,13C6-Phe and 13C9-Phe). Morphometry and cell proliferation also were measured in the jejunum and ileum. Neither dose of IGF-I affected the masses of wet tissue, protein or DNA, or the villus height, cell proliferation or LPH-specific activity. Oral IGF-I decreased the synthesis and abundance of prolactase-phlorizin hydrolase (pro-LPH), but increased brush-border (BB)-LPH synthesis in the ileum. The BB-LPH processing efficiency was twofold to threefold greater in IGF-fed than in control pigs. In all pigs, villus height and the total mucosal and specific activity of LPH activity were greater in the ileum than in the jejunum, yet the synthesis of BB-LPH were significantly lower in the ileum than in the jejunum. We conclude that oral IGF-I increases the processing efficiency of pro-LPH to BB-LPH but does not affect LPH activity. Moreover, the posttranslational processing of BB-LPH is markedly lower in the ileum than in the jejunum.