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Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic β cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 4/29/2003, Vol. 100 Issue 9, p5187. 6p. 3 Color Photographs, 1 Black and White Photograph, 17 Graphs. - Publication Year :
- 2003
-
Abstract
- Insulin secretion is controlled by the β cell's metabolic state, and the ability of the secretory granules to undergo exocytosis increases during glucose stimulation in a membrane potential-independent fashion. Here, we demonstrate that exocytosis of insulincontaining secretory granules depends on phosphatidylinositol 4-kinase (PI 4-kinase) activity and that inhibition of this enzyme suppresses glucose-stimulated insulin secretion. Intracellular application of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P[sub 2]] stimulated exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in a readily releasable pool. Reducing the cytoplasmic ADP concentration in a way mimicking the effects of glucose stimulation activated PI 4-kinase and increased exocytosis whereas changes of the ATP concentration in the physiological range had little effect. The PI(4,5)P[sub 2]-binding protein Ca[sup 2+]-dependent activator protein for secretion (CAPS) is present in β cells, and neutralization of the protein abolished both Ca[sup 2+]- and PI(4,5)P[sub 2]-induced exocytosis. We conclude that ADPinduced changes in PI 4-kinase activity, via generation of PI(4,5)P[sub 2], represents a metabolic sensor in the β cell by virtue of its capacity to regulate the release competence of the secretory granules. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PANCREATIC beta cells
*EXOCYTOSIS
*INSULIN
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 100
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 9800417
- Full Text :
- https://doi.org/10.1073/pnas.0931282100