| Porcine glucagon-like peptide-2: structure, signaling, metabolism and effects. | |
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MedLine Citation:
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PMID: 18164496 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mass spectrometry of HPLC-purified porcine glucagon-like peptide-2 (pGLP-2)(1) revealed a 35 amino acid sequence with C-terminal Ser and Leu, in contrast to the 33 amino acids of human, cow, rat and mouse GLP-2. Synthetic pGLP-2 stimulated cAMP-production in COS-7 cells expressing human GLP-2 (hGLP-2) receptor with the same potency and efficacy as hGLP-2. In anesthetized pigs (n=9) given intravenous pGLP-2 infusions, the half life (t1/2) of intact pGLP-2 (8.4+/-0.9 min) was shorter (p<0.01) than that of the primary metabolite pGLP-2 (3-35) (34.0+/-5.2 min), generated by dipeptidyl peptidase-4 (DPP-4) cleavage. Adding the DPP-4 inhibitor valine-pyrrolidide prolonged t1/2 of intact pGLP-2 (p<0.05). The metabolic clearance rate (MCR) of intact pGLP-2 (23.9+/-3.82 mL/(kg x min)) was greater (p<0.0001) than that of pGLP-2 (3-35) (6.36+/-1.45 mL/(kg x min)) and larger than the previously reported MCR of hGLP-2 in pig. The MCR of intact pGLP-2 was reduced by valine-pyrrolidide (p<0.05), but was still greater than that of intact hGLP-2 previously reported. In the isolated perfused porcine pancreas, pGLP-2 stimulated glucagon release (p<0.05), but had no effect on insulin or somatostatin release. Exocrine secretion was unaffected and there was no apparent vasoactive effect. In mice (n=8), both subcutaneous hGLP-2 and pGLP-2 given twice daily for 10 days, significantly and equally increased small intestinal weight, length and cross-sectional area of proximal ileum. In conclusion, pGLP-2 and hGLP-2 have similar effects in vivo and in vitro in spite of the structural differences. However, pGLP-2 is cleared more rapidly in pigs than hGLP-2. |
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Authors:
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Nis B Pedersen; Karina R Hjollund; Anders H Johnsen; Cathrine Orskov; Mette M Rosenkilde; Bolette Hartmann; Jens J Holst |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-11-28 |
Journal Detail:
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Title: Regulatory peptides Volume: 146 ISSN: 0167-0115 ISO Abbreviation: Regul. Pept. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-01-21 Completed Date: 2008-05-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100479 Medline TA: Regul Pept Country: Netherlands |
Other Details:
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Languages: eng Pagination: 310-20 Citation Subset: IM |
Affiliation:
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Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Cattle Glucagon-Like Peptide 2 / blood, genetics*, metabolism* Humans Intestinal Mucosa / metabolism Mice Molecular Sequence Data Rats Sequence Alignment Signal Transduction / physiology Swine |
| Chemical | |
Reg. No./Substance:
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0/Glucagon-Like Peptide 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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