Intestinal transport of insulin-like growth factor-I (igf-I) in the suckling rat.
OBJECTIVE
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 x 10 cpm of rh I-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.
Philipps
Anthony F
AF
Department of Pediatrics, University of California Davis, Sacramento 95817, USA. a.philipps@ucdmc.ucdavis.edu
Kling
Pamela J
PJ
Grille
James G
JG
Dvorák
Bohuslav
B
D000818:Animals; D000833:Animals, Suckling; D002850:Chromatography, Gel; D004064:Digestive System / Q000378:metabolism* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D007457:Iodine Radioisotopes; D007583:Jejunum / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D007457:Iodine Radioisotopes; D007334:Insulin-Like Growth Factor I