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Phosphatidylinosito...
Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells
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Olsen, HL (författare)
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Hoy, M (författare)
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Zhang, W (författare)
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visa fler...
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- Bertorello, AM (författare)
- Karolinska Institutet
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Bokvist, K (författare)
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Capito, K (författare)
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Efanov, AM (författare)
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Meister, B (författare)
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Thams, P (författare)
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- Yang, SN (författare)
- Karolinska Institutet
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- Rorsman, Patrik (författare)
- Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Berggren, PO (författare)
- Karolinska Institutet
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Gromada, J (författare)
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(creator_code:org_t)
- 2003-04-16
- 2003
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 100:9, s. 5187-5192
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http://dx.doi.org/10... (free)
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http://www.pnas.org/...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- insulin
- Ca2+-dependent activator protein for secretion (CAPS)
- exocytosis
- phosphoinositides
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Olsen, HL
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Hoy, M
-
Zhang, W
-
Bertorello, AM
-
Bokvist, K
-
Capito, K
-
visa fler...
-
Efanov, AM
-
Meister, B
-
Thams, P
-
Yang, SN
-
Rorsman, Patrik
-
Berggren, PO
-
Gromada, J
-
visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Proceedings of t ...
- Av lärosätet
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Lunds universitet
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Karolinska Institutet