AJP - Endo Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab (March 18, 2003). doi:10.1152/ajpendo.00086.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/1/E73    most recent
00086.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Juhl, K.
Right arrow Articles by Gromada, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Juhl, K.
Right arrow Articles by Gromada, J.
Submitted on February 24, 2003
Accepted on March 11, 2003

Cytoplasmic phospholipase A2-mediated formation of arachidonic acid and lysophospholipids are required for Ca2+-dependent exocytosis in mouse pancreatic {beta}-cells

Kirstine Juhl1, Marianne Hoy1, Hervor L. Olsen1, Krister Bokvist2, Alexander M. Efanov2, Else K. Hoffmann3, and Jesper Gromada2*

1 Laboratory of Islet Cell Physiology, Novo Nordisk A/S, Bagsvaerd, Denmark
2 Laboratory of Islet Cell Physiology, Novo Nordisk A/S, Bagsvaerd, Denmark; Department of Beta Cell Biology, Lilly Research Laboratories, Hamburg, Germany
3 Department of Biological Chemistry, The August Krogh Institute, University of Copenhagen, Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: gromada_jesper{at}lilly.com.

Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2{alpha}) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic {beta}-cells. cPLA2{alpha} dose-dependently (EC50=86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole-cell Ca2+-current or cytoplasmic Ca2+ levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules from 70-80 to 280-300. cPLA2{alpha}-stimulated exocytosis was antagonised by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or antisense oligonucleotide against cPLA2{alpha}. The action of cPLA2{alpha} was mimicked by a combination of arachidonic acid and lysophosphatidylcholine (470% stimulation) where each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2{alpha} was inhibited by the Cl- channel inhibitor DIDS and in cells pretreated with ClC-3 Cl- channel antisense oligonucleotides. We propose that cPLA2{alpha} plays an important role in controlling the rate of exocytosis in {beta}-cells. This effect of cPLA2{alpha} reflects an enhanced transgranular Cl- flux leading to an increase in the number of granules available for release and requires the combined actions of arachidonic acid and lysophosphatidylcholine.




This article has been cited by other articles:


Home page
 J. Physiol.Home page
F. Darios, E. Connell, and B. Davletov
Phospholipases and fatty acid signalling in exocytosis
J. Physiol., December 15, 2007; 585(3): 699 - 704.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. J. Nolan, M. S.R. Madiraju, V. Delghingaro-Augusto, M.-L. Peyot, and M. Prentki
Fatty Acid Signaling in the {beta}-Cell and Insulin Secretion
Diabetes, December 1, 2006; 55(Supplement_2): S16 - S23.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
H. M. Milne, C. J. Burns, P. E. Squires, N. D. Evans, J. Pickup, P. M. Jones, and S. J. Persaud
Uncoupling of Nutrient Metabolism From Insulin Secretion by Overexpression of Cytosolic Phospholipase A2
Diabetes, January 1, 2005; 54(1): 116 - 124.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.