Document Detail

Apolipoprotein A-V modulates insulin secretion in pancreatic beta-cells through its interaction with midkine.
MedLine Citation:
PMID:  19910685     Owner:  NLM     Status:  MEDLINE    
Apolipoprotein A-V is an important determinant of plasma triglyceride level in both humans and mice. This study showed the physiological impact of apoA-V on insulin secretion in rat pancreatic beta-cells (INS-1 cells). In order to precise the mechanism of action, binding experiments coupled to mass spectrometry were performed to identify a potential membrane receptor. Results showed an interaction between apoA-V and midkine protein. Confocal microscopy confirmed the plasma membrane co-localisation of this two-proteins after the treatment of INS-1 cells with the apo-AV recombinant protein and indicated that the cell surface midkine could be involved in apoA-V endocytosis, since these two proteins were co-translocated at the plasma membrane or in the cytosol compartment. This co-localisation is correlated with an increase in insulin secretion in a dose dependant manner during short incubation period. Reduction of midkine expression by small interfering RNA duplexes revealed a decrease in the ability of these transfected cells to secrete insulin in presence of apoA-V. Competition experiments for the apoA-V-midkine binding at the cell surface using antibody directed against midkine is able to influence INS-1 cell function as insulin secretion. Our results showed apoA-V ability to enhance insulin secretion in beta-cells and provide evidence of an internalization pathway involving the midkine as partner.
Audrey Helleboid-Chapman; Maxime Nowak; Stéphane Helleboid; Emmanuelle Moitrot; Corinne Rommens; Hélène Dehondt; Laurent Héliot; Hervé Drobecq; Jamila Fruchart-Najib; Jean-Charles Fruchart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-04
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  24     ISSN:  1421-9778     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2009  
Date Detail:
Created Date:  2009-11-13     Completed Date:  2010-02-17     Revised Date:  2011-05-06    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  451-60     Citation Subset:  IM    
Copyright Information:
2009 S. Karger AG, Basel.
Université Lille Nord de France, Inserm, UDSL and Institut Pasteur de Lille, France.
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MeSH Terms
Amino Acid Sequence
Apolipoproteins / analysis,  metabolism*
Cell Line, Tumor
Cytokines / analysis,  genetics,  metabolism*
Insulin / secretion*
Insulin-Secreting Cells / metabolism*
Molecular Sequence Data
Protein Binding
RNA, Small Interfering / metabolism
Recombinant Proteins / metabolism,  pharmacology
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Reg. No./Substance:
0/Apoa5 protein, rat; 0/Apolipoproteins; 0/Cytokines; 0/RNA, Small Interfering; 0/Recombinant Proteins; 11061-68-0/Insulin; 137497-38-2/midkine

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