Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats

Toshikiro Kimura, Yusuke Murakawa, Misako Ohno, Seiji Ohtani, Kazutaka Higaki

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Abstract

The GI absorption of recombinant human insulin-like growth factor-I (rhIGF-I) and its improvement were investigated in rats. The 125I-rhIGF-I rapidly degraded to the trichloroacetic acid-soluble form in the small- intestinal contents, but it was relatively stable in the gastric and large- intestinal contents and in the subcellular fraction of the small-intestinal mucosa. To protect rhIGF-I from degradation in the small-intestinal contents, the effect of some adjuvants was examined and their degradation was markedly inhibited by the presence of aprotinin or casein. After p.o. administration of 125I-rhIGF-I at the dose of 1.0 mg/kg, trichloroacetic acid- precipitable radioactivity in the plasma was periodically determined. We found that a considerable amount of rhIGF-I was absorbed into the systemic circulation and that the bioavailability was 9.3%, which is much greater than that of insulin. The coadministration of aprotinin and that of casein enhanced the bioavailability further: 46.9% and 67.0%, respectively. Radioimmunoassay using a monoclonal antibody for rhIGF-I confirmed the high bioavailability of immunoreactive rhIGF-I. From gel chromatography of plasma, the radioactivity in the plasma was found to be in the form of high- molecular-weight complexes. The mechanism for the uptake of rhIGF-I by intestinal mucosa may be absorptive-mediated endocytosis.

Original languageEnglish
Pages (from-to)611-618
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume283
Issue number2
Publication statusPublished - Nov 1997

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Insulin-Like Growth Factor I
Gastrointestinal Contents
Biological Availability
Trichloroacetic Acid
Aprotinin
Intestinal Mucosa
Caseins
Radioactivity
Subcellular Fractions
Endocytosis
Gastrointestinal Absorption
Radioimmunoassay
Gel Chromatography
Stomach
Molecular Weight
Monoclonal Antibodies
Insulin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats. / Kimura, Toshikiro; Murakawa, Yusuke; Ohno, Misako; Ohtani, Seiji; Higaki, Kazutaka.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 283, No. 2, 11.1997, p. 611-618.

Research output: Contribution to journalArticle

Kimura, Toshikiro ; Murakawa, Yusuke ; Ohno, Misako ; Ohtani, Seiji ; Higaki, Kazutaka. / Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats. In: Journal of Pharmacology and Experimental Therapeutics. 1997 ; Vol. 283, No. 2. pp. 611-618.
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