Appearance of receptor active Insulin-like Growth Factor-I (IGF-I) in blood after feeding in the suckling rat

Anthony F Philipps, B. Dvorak, P. J. Kling, J. Grille, O. Koldovsky

Research output: Contribution to journalArticle

Abstract

Insulin-Like Growth Factor-I (IGF-I) is a potent mitogenic peptide believed to be involved in postnatal growth regulation. In addition to endogenous production, sucklings of many species, including the rat, ingest significant quantities of IGF-I in breast milk. In recent work from our laboratory, we have demonstrated that sucklings fed an artifical diet + IGF-I had serum IGF-I levels similar to dam fed controls and 2X that of animals fed the artificial diet alone. We examined the hypothesis that (GF's may be absorbed in bioactive form from the gastrointestinal tract to the portal circulation and beyond. The experimental design consisted of using fasted suckling rats of 10 days of age (n=22). Radiolabelled rhIGF-I (4x106 cpm, 100 μl volume) was given in a 1:1 mixture of appropriate aged rat milk via orogastric tube at time "0." At 5, 10, 20, and 30 minutes post administration, portal blood was obtained by venipuncture while under anesthesia. Within 30-60 seconds after portal venipuncture, cardiac ("peripheral") blood was also removed. Blood specimens were weighed to determine volume and counted in a gamma counter to determine radioactivity (cpm). Results are expressed as per 100μl of blood to account for differences in volume of blood obtained during venipuncture. Results: show that IGF-I radioactivity in portal blood was higher than in peripheral blood and peaked at 20 min post ingestion. Size exclusion gel chromatography was performed on all samples and confirmed that 30-40% of cpm eluted in the position of "native" IGF-I. HPLC performed on selected peaks from portal blood was identical to the elution position of rhIGF-I. In addition, selected peak fractions from portal blood isolates were exposed to competitive binding assays using a crude placental membrane preparation bearing IGF-I receptors. This assay confirmed the presence of receptor active IGF-I in portal blood samples from animals fed the radiolabelled IGF-I preparation. We conclude that IGF-I is absorbed in a receptor active form from the gastrointestinal tract of the suckling rat. Furthermore, since we have previously demonstrated that intravenously injected IGF-I passes into bile in a receptor active form in the infant rat, this latter series of studies would also lend credence to the concept of an enterohepatic circulation for IGF in the suckling.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Feb 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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