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Articles

Oral IGF-I Alters the Posttranslational Processing but Not the Activity of Lactase-Phlorizin Hydrolase in Formula-Fed Neonatal Pigs^{1 ,2}

Douglas G. Burrin^*3, Barbara Stoll^*, Ming Z. Fan^*,4, Mary A. Dudley, Sharon M. Donovan and Peter J. Reeds^**

^* U. S. Department of Agriculture Agricultural Research Service, Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030; Division of Physiology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; and Departments of ^** Animal Sciences and Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801

³To whom correspondence should be addressed. E-mail: dburrin{at}bcm.tmc.edu

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.

KEY WORDS: • protein degradation • cell proliferation • growth factor • protein synthesis • disaccharidase • pigs

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