|Burrin, Douglas - Doug|
Submitted to: Journal of Pediatric Gastroenterology and Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/7/2001
Publication Date: 8/1/2001
Citation: Park,K.Y., Dudley,M.A., Burrin,D.G., Donovan,S.N. 2001. Intestinal protein and LPH synthesis in parenterally fed piglets receiving partial enteral nutrition and enteral insulinlike growth factor 1. Journal of Pediatric Gastroenterology and Nutrition. 33(2):189-195. Interpretive Summary: Premature infants are often fed intravenously because they cannot tolerate normal oral feeding. As a result, these infants are usually fed very small amounts of food into their intestine, called partial enteral nutrition. Previous studies showed that adding a hormone, called insulin-like growth factor I (IGF-I), to these partial enteral feedings stimulates the activity of an intestinal enzyme that digests the milk sugar, lactose; the enzyme is called lactase. The aim of this study was to use newborn piglets as a model for human infants and determine the mechanism of how feeding IGF-I affects the activity of intestinal lactase. Newborn pigs were fed partial enteral nutrition supplemented with and without IGF-I for seven days. Then the piglets were infused with a specially tagged amino acid that allowed us to measure how lactase is produced in the intestinal cells. We found that IGF-I increased both the growth and lactase activity in the intestine. Also, we found that IGF-I increased the amount of lactase protein, but did not affect the production of the lactase gene. The increase in the amount of the lactase protein was due to a reduction in the rate of breakdown of the protein, because the rate of synthesis was not affected by IGF-I.
Technical Abstract: Providing partial enteral nutrition (PEN) supplemented with insulinlike growth factor-1 (IGF-1) to parenterally fed piglets increases lactase-phlorizin hydrolase (LPH) activity, but not LPH mRNA. The current aim was to investigate potential mechanisms by which IGF-1 up-regulates LPH activity. Newborn piglets (n = 15) received 100% parenteral nutrition (TPN), 80% parenteral nutrition + 20% parenteral nutrition (PEN), or PEN + IGF-1 (1.0 mg. kg-1. d-1) for 7 days. On day 7, [2H3]-leucine was intravenously administered to measure mucosal protein and brush border LPH (BB LPH) synthesis. Weight gain, nutrient intake, and jejunal weight and length were similar among the treatment groups. Partial enteral nutrition alone increased mucosal weight, villus width and cross-sectional area, LPH activity, mRNA expression, and high mannose LPH precursor (proLPHh) abundance compared with TPN (P<0.05). Insulinlike growth factor-1 further increased mucosal weight, LPH activity, and LPH activity per unit BB LPH approximately twofold over PEN alone (P < 0.05) but did not affect LPH mRNA or the abundance of proLPHh (one of the LPH isoforms) or mature LPH. Isotopic enrichment of [2H3]-leucine in plasma, mucosal protein, and LPH precursors, and the fractional and absolute synthesis rates of mucosal protein and LPH were similar among the treatment groups. Insulinlike growth factor-1 treatment increased total mucosal protein synthesis (60%, P < 0.05) but not LPH synthesis compared with the other two groups. Because IGF-1 did not affect the fractional synthesis rate of either mucosal protein or LPH, the authors suggest that enteral IGF-1 increases mucosal protein mass and LPH activity by suppressing mucosal proteolytic degradation.