Document Detail


Brevinin-2-related peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet.
MedLine Citation:
PMID:  20496306     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cationic, alpha-helical frog skin antimicrobial peptide B2RP (brevinin-2-related peptide) shows sequence similarity to antimicrobial peptides belonging to the brevinin-2 family, but lacks the C-terminal cyclic heptapeptide domain (Cys-Lys-Xaa (4)-Cys). Synthetic B2RP produced a significant (p<0.05) stimulation of insulin release (148% of basal rate at a concentration of 1 muM with a maximum response of 222% of basal rate at a concentration of 3 muM) from BRIN-BD11 clonal beta-cells without increasing the release of the cytosolic enzyme, lactate dehydrogenase. Increasing cationicity of B2RP while maintaining amphipathicity by the substitution Asp (4) --> Lys enhanced the insulin-releasing potency (137% of basal rate at a concentration of 0.3 muM; p<0.05) with no stimulation of lactate dehydrogenase release. In contrast, the L18K, and D4K, L18K analogues were toxic to the cells, and the K16A analogue, with increased amphipathicity and hydrophobicity, showed reduced potency. Administration of [D4K]B2RP (100 nmol/kg body weight) to mice fed a high fat diet to induce obesity and insulin-resistance significantly (p<0.05) enhanced insulin release and improved glucose tolerance during the 60-minute period following an intraperitoneal glucose load (18 mmol/kg body weight). B2RP shows potential for development into an agent for the treatment of type 2 diabetes.
Authors:
Y H A Abdel-Wahab; S Patterson; P R Flatt; J M Conlon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-21
Journal Detail:
Title:  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme     Volume:  42     ISSN:  1439-4286     ISO Abbreviation:  Horm. Metab. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0177722     Medline TA:  Horm Metab Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  652-6     Citation Subset:  IM    
Copyright Information:
Copyright Georg Thieme Verlag KG Stuttgart New York.
Affiliation:
School of Biomedical Sciences, University of Ulster, N. Ireland, UK.
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MeSH Terms
Descriptor/Qualifier:
Amphibian Proteins / chemistry,  pharmacology*
Animals
Antimicrobial Cationic Peptides / chemistry,  pharmacology*
Cell Death / drug effects
Diet
Dietary Fats / administration & dosage*,  pharmacology*
Feeding Behavior / drug effects*
Glucose Tolerance Test
Insulin / blood,  secretion*
Insulin Resistance
Insulin-Secreting Cells / drug effects,  pathology,  secretion
L-Lactate Dehydrogenase / metabolism
Mice
Obesity / physiopathology
Oligopeptides / pharmacology*
Chemical
Reg. No./Substance:
0/Amphibian Proteins; 0/Antimicrobial Cationic Peptides; 0/Dietary Fats; 0/Oligopeptides; 0/trypsinogen activation peptide; 11061-68-0/Insulin; 145963-50-4/brevinin-2, Rana; EC 1.1.1.27/L-Lactate Dehydrogenase

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


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