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- Title
Apolipoprotein A-V Modulates Insulin Secretion in Pancreatic β-cells Through its Interaction with Midkine.
- Authors
Helleboid-Chapman, Audrey; Nowak, Maxime; Helleboid, Stéphane; Moitrot, Emmanuelle; Rommens, Corinne; Dehondt, Hélène; Héliot, Laurent; Drobecq, Hervé; Fruchart-Najib, Jamila; Fruchart, Jean-Charles
- Abstract
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 β-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 β-cells and provide evidence of an internalization pathway involving the midkine as partner. Copyright © 2009 S. Karger AG, Basel
- Subjects
APOLIPOPROTEINS; INSULIN; PANCREATIC secretions; CELL physiology; RATS; MASS spectrometry
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2009, Vol 24, Issue 5/6, p451
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000257484