Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 23 November 2007:
Vol. 318. no. 5854, pp. 1299 - 1302
DOI: 10.1126/science.1146824
Prev | Table of Contents | Next

Reports

Requirement of Inositol Pyrophosphates for Full Exocytotic Capacity in Pancreatic β Cells

Christopher Illies,1 Jesper Gromada,2 Roberta Fiume,1 Barbara Leibiger,1 Jia Yu,1 Kirstine Juhl,3 Shao-Nian Yang,1 Deb K. Barma,4 John R. Falck,4 Adolfo Saiardi,5 Christopher J. Barker,1* Per-Olof Berggren1

Inositol pyrophosphates are recognized components of cellular processes that regulate vesicle trafficking, telomere length, and apoptosis. We observed that pancreatic β cells maintain high basal concentrations of the pyrophosphate diphosphoinositol pentakisphosphate (InsP7 or IP7). Inositol hexakisphosphate kinases (IP6Ks) that can generate IP7 were overexpressed. This overexpression stimulated exocytosis of insulin-containing granules from the readily releasable pool. Exogenously applied IP7 dose-dependently enhanced exocytosis at physiological concentrations. We determined that IP6K1 and IP6K2 were present in β cells. RNA silencing of IP6K1, but not IP6K2, inhibited exocytosis, which suggests that IP6K1 is the critical endogenous kinase. Maintenance of high concentrations of IP7 in the pancreatic β cell may enhance the immediate exocytotic capacity and consequently allow rapid adjustment of insulin secretion in response to increased demand.

1 The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
2 Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
3 Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
5 U.K. Medical Research Council (MRC) Cell Biology Unit and Laboratory for Molecular Cell Biology, Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.

* To whom correspondence should be addressed. E-mail: chris.barker{at}ki.se

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Nucleolus Exhibits an Osmotically Regulated Gatekeeping Activity That Controls the Spatial Dynamics and Functions of Nucleolin.
L. Yang, J. M. Reece, J. Cho, C. D. Bortner, and S. B. Shears (2008)
J. Biol. Chem. 283, 11823-11831
   Abstract »    Full Text »    PDF »
Highlights From The Literature.
(2008)
Physiology 23, 61-63
   Full Text »    PDF »
Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis.
R. Bhandari, K. R. Juluri, A. C. Resnick, and S. H. Snyder (2008)
PNAS 105, 2349-2353
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)