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Intestinal Transport of Insulin-Like Growth Factor-I (IGF-I) in the Suckling Rat

Philipps, Anthony F.*; Kling, Pamela J.†; Grille, James G.†; Dvořák, Bohuslav†

Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Abstract

Objectives: Insulin-Like Growth Factor-1 is a potent growth-promoting peptide that is present in mammalian milk. Previous studies have suggested that milk-borne IGF-1 may be absorbed intact from the gastrointestinal tract of the suckling but the mechanism responsible for such transport is not well documented. The present study was designed to investigate in an in vivo suckling rat model whether or not intestinal absorption of IGF-1 is a saturable phenomenon.

Methods: Suckling rats (10–12 days postnatal age) were studied under anesthesia. A jejunal loop from each rat pup was isolated and injected intraluminally with 1–2 × 105 cpm of rh125I-IGF-I. Injections were performed in paired littermates either with or without a preceding injection of unlabeled IGF-I of 20, 500, or 1000 ng/ml concentration. After flushing, the loops and livers were homogenized and counted in a gamma counter. In addition, homogenates of jejunum and liver were precipitated with trichloroacetic acid (TCA) and the precipitates also counted. In selected instances (jejunum), acid gel chromatography of homogenates was also performed.

Results: Retention of radioactivity was observed in all jejunal specimens, but the pre-incubation of jejunal loops with unlabeled IGF-1 was associated with a biphasic response, i.e. at low dose (20 ng/ml) pre-incubation limited retention of radioactivity, but at a high dose (1000 ng/ml), retention was enhanced (P < 0.05). Linear regression analysis confirmed this inverse relationship. Liver radioactivity followed a similar pattern. Between 40 and 49% of the radioactivity in jejunal and liver homogenates was TCA precipitable. Chromatography of jejunal homogenates showed that approximately 40% of cpm migrated in a position identical with that of intact IGF-1.

Conclusions: The intestinal uptake of IGF-1 in the suckling is nonsaturable, confirming previous in vitro studies and suggesting that a nonreceptor-dependent method of transepithelial transport is important in this process.

Author Information

*Department of Pediatrics, University of California Davis, Sacramento, California, U.S.A., and †Furrow Research Laboratory, Cosden Neonatal Research Wing, Steele Memorial Children's Research Center, University of Arizona College of Medicine, Tucson, Arizona, U.S.A.

Address for correspondence: Anthony F. Philipps, M.D., Department of Pediatrics, University of California Davis Medical Center, 2516 Stockton Blvd Sacramento, CA 95817 (e-mail: a.philipps@ucdmc.ucdavis.edu).

This work was supported by funds from the National Institutes of Health (NICHD) P01 HD26013, the University of California Davis Health System and the Armstrong-McDonald Foundation.

© 2002 Lippincott Williams & Wilkins, Inc.