| In vivo and in vitro degradation of glucagon-like peptide-2 in humans. | |
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MedLine Citation:
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PMID: 10946898 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucagon-like peptide-2 (GLP-2), an intestinal product of glucagon gene expression which induces intestinal growth in mice, has been proposed as a treatment for intestinal insufficiency. GLP-2 is metabolized extensively by dipeptidyl peptidase IV (DPP-IV) in rats, but less is known about its fate in humans. Therefore, GLP-2 metabolism was investigated in healthy volunteers after 1) a 500-Cal mixed meal (n = 6), 2) iv infusion of synthetic human GLP-2 (0.8 pmol/kg x min; n = 8), 3) a sc bolus injection (400 microg; n = 9), and 4) in vitro incubation in plasma and blood (1,000 pmol/L; n = 4). GLP-2 concentrations were determined by N-terminal RIA measuring only intact GLP-2, side-viewing RIA measuring intact and degraded forms [e.g. GLP-2-(3-33) arising from DPP-IV degradation], and high performance liquid chromatography (HPLC). Meal ingestion elevated plasma GLP-2 (intact, 16 +/- 3 to 73 +/- 10 pmol/L at 90 min), and HPLC revealed two immunoreactive components: intact GLP-2 (57 +/- 2%) and GLP-2-(3-33). GLP-2 infusion increased plasma levels [intact, 9 +/- 4 to 131 +/- 11 pmol/L; total, 23 +/- 7 to 350 +/- 18 pmol/L; the differences represent GLP-2-(3-33)]. The elimination t(1/2) values were 7.2 +/- 2 min (intact GLP-2) and 27.4 +/- 5.4 min [GLP-2-(3-33)], and MCRs were 6.8 +/- 0.6 and 1.9 +/- 0.3 mL/kg x min, respectively. Subcutaneous injection increased intact GLP-2 to maximally 1,493 +/- 250 pmol/L at 45 min, whereas total GLP-2 increased to 2,793 +/- 477 pmol/L at 90 min. At 60 min, plasma contained 69 +/- 1% intact GLP-2. In vitro the t(1/2) values were 8.0 +/- 1.5 h (plasma) and 3.3 +/- 0.3 h (blood). GLP-2-(3-33) was the only degradation product identified by HPLC, and a DPP-IV inhibitor abolished the degradation of GLP-2 in vitro. We conclude that GLP-2 is extensively degraded to GLP-2-(3-33) in humans, presumably by DPP-IV. Nevertheless, 69% remains intact 1 h after GLP-2 injection, supporting the possibility of sc use in patients with intestinal insufficiency. |
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Authors:
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B Hartmann; M B Harr; P B Jeppesen; M Wojdemann; C F Deacon; P B Mortensen; J J Holst |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 85 ISSN: 0021-972X ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2000 Aug |
Date Detail:
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Created Date: 2000-08-31 Completed Date: 2000-08-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2884-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Female Glucagon-Like Peptide 2 Glucagon-Like Peptides Humans Infusions, Intravenous Injections, Subcutaneous Kinetics Male Mice Middle Aged Peptide Fragments / administration & dosage, blood, metabolism* Peptides / administration & dosage, blood, metabolism* Postprandial Period Rats Recombinant Proteins / administration & dosage, blood, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Glucagon-Like Peptide 2; 0/Peptide Fragments; 0/Peptides; 0/Recombinant Proteins; 62340-29-8/Glucagon-Like Peptides |
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