Document Detail


Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety.
MedLine Citation:
PMID:  20631047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) have received much attention regarding possible roles in aetiology and treatment of type 2 diabetes. However, peptides co-secreted from the same enteroendocrine cells are less well studied. The present investigation was designed to characterise the in vitro and in vivo effects of xenin, a peptide co-secreted with GIP from intestinal K-cells. We examined the enzymatic stability, insulin-releasing activity and associated cAMP production capability of xenin in vitro. In addition, the effects of xenin on satiety, glucose homoeostasis and insulin secretion were examined in vivo. Xenin was time dependently degraded (t(1/2)=162±6 min) in plasma in vitro. In clonal BRIN-BD11 cells, xenin stimulated insulin secretion at 5.6 mM (P<0.05) and 16.7 mM (P<0.05 to P<0.001) glucose levels compared to respective controls. Xenin also exerted an additive effect on GIP, GLP1 and neurotensin-mediated insulin secretion. In clonal β-cells, xenin did not stimulate cellular cAMP production, alter membrane potential or elevate intra-cellular Ca(2)(+). In normal mice, xenin exhibited a short-acting (P<0.01) satiety effect at high dosage (500 nmol/kg). In overnight fasted mice, acute injection of xenin enhanced glucose-lowering and elevated insulin secretion when injected concomitantly or 30 min before glucose. These effects were not observed when xenin was administered 60 min before the glucose challenge, reflecting the short half-life of the native peptide in vivo. Overall, these data demonstrate that xenin may have significant metabolic effects on glucose control, which merit further study.
Authors:
Ashley I Taylor; Nigel Irwin; Aine M McKillop; Steven Patterson; Peter R Flatt; Victor A Gault
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-14
Journal Detail:
Title:  The Journal of endocrinology     Volume:  207     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-15     Completed Date:  2010-10-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  87-93     Citation Subset:  IM    
Affiliation:
SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences Research Institute, University of Ulster, Coleraine, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / metabolism*
Cell Line
Eating / drug effects,  physiology
Gastrointestinal Hormones / administration & dosage,  pharmacology*,  physiology*
Insulin / secretion*
Insulin-Secreting Cells / drug effects,  secretion
Mice
Neurotensin / administration & dosage,  pharmacology*,  physiology*
Protein Stability
Satiety Response / drug effects*,  physiology*
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Gastrointestinal Hormones; 11061-68-0/Insulin; 144092-28-4/xenin 25; 39379-15-2/Neurotensin

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