Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells
(2003) In Proceedings of the National Academy of Sciences 100(9). p.5187-5192- Abstract
- Insulin secretion is controlled by the beta 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 insulin-containing 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 phosphaticlylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P-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... (More)
- Insulin secretion is controlled by the beta 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 insulin-containing 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 phosphaticlylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P-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-2-binding protein Ca2+-dependent activator protein for secretion (CAPS) is present in beta cells, and neutralization of the protein abolished both Ca2+- and PI(4,5)P-2-induced exocytosis. We conclude that ADP-induced changes in PI 4-kinase activity, via generation of Pl(4,5)P-2, represents a metabolic sensor in the beta cell by virtue of its capacity to regulate the release competence of the secretory granules. (Less)
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https://lup.lub.lu.se/record/312419
- author
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- insulin, Ca2+-dependent activator protein for secretion (CAPS), exocytosis, phosphoinositides
- in
- Proceedings of the National Academy of Sciences
- volume
- 100
- issue
- 9
- pages
- 5187 - 5192
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000182612600042
- pmid:12700357
- scopus:0038303159
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0931282100
- language
- English
- LU publication?
- yes
- id
- f5287eda-7d52-48dd-aff8-886afdf78ff3 (old id 312419)
- date added to LUP
- 2016-04-01 12:34:11
- date last changed
- 2022-03-21 06:05:32
@article{f5287eda-7d52-48dd-aff8-886afdf78ff3,
abstract = {{Insulin secretion is controlled by the beta 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 insulin-containing 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 phosphaticlylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P-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-2-binding protein Ca2+-dependent activator protein for secretion (CAPS) is present in beta cells, and neutralization of the protein abolished both Ca2+- and PI(4,5)P-2-induced exocytosis. We conclude that ADP-induced changes in PI 4-kinase activity, via generation of Pl(4,5)P-2, represents a metabolic sensor in the beta cell by virtue of its capacity to regulate the release competence of the secretory granules.}},
author = {{Olsen, HL and Hoy, M and Zhang, W and Bertorello, AM and Bokvist, K and Capito, K and Efanov, AM and Meister, B and Thams, P and Yang, SN and Rorsman, Patrik and Berggren, PO and Gromada, J}},
issn = {{1091-6490}},
keywords = {{insulin; Ca2+-dependent activator protein for secretion (CAPS); exocytosis; phosphoinositides}},
language = {{eng}},
number = {{9}},
pages = {{5187--5192}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells}},
url = {{http://dx.doi.org/10.1073/pnas.0931282100}},
doi = {{10.1073/pnas.0931282100}},
volume = {{100}},
year = {{2003}},
}