Oral IGF-l alters the posttranslational processing but not the activity oflactase-phlorizin hydrolase in formula-fed neonatal pigs

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 me asured in vivo in fed pigs using a 6-h intravenous, overlapping infusion of multiple stable isotopes (H-2(3)-Leu,C-13(1)-Leu,C-13(1)-Phe, H-2(5)-Phe, C-13(6)-Phe and C-13(g)-Phe). Morphometry and cell proliferation also were measured in the jejunum and ileum. Neither dose of IGF-l affected the masse s of wet tissue, protein or DNA, or the villus height, cell proliferation o r LPH-specific activity. Oral IGF-I decreased the synthesis and abundance o f prolactase-phlorizin hydrolase (pro-LPH), but increased brush-border (BB) -LPH synthesis in the ileum. The BB-LPH processing efficiency was twofold t o threefold greater in IGF-fed than in control pigs. In all pigs, villus he ight and the total mucosal and specific activity of LPH activity were great er in the ileum than in the jejunum, yet the synthesis of BB-LPH were signi ficantly lower in the ileum than in the jejunum. We conclude that oral IGF- l increases the processing efficiency of pro-LPH to BB-LPH but does not aff ect LPH activity. Moreover, the posttranslational processing of BB-LPH is m arkedly lower in the ileum than in the jejunum.