Document Detail


Porcine glucagon-like peptide-2: structure, signaling, metabolism and effects.
MedLine Citation:
PMID:  18164496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-28
Journal Detail:
Title:  Regulatory peptides     Volume:  146     ISSN:  0167-0115     ISO Abbreviation:  Regul. Pept.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-21     Completed Date:  2008-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100479     Medline TA:  Regul Pept     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  310-20     Citation Subset:  IM    
Affiliation:
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Glucagon-Like Peptide 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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