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Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells
Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. Furthermore, of the different PI3Ks, the class II isoforms were detected in β cells, although their role is still not well understo...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Society for Biochemistry and Molecular Biology
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039383/ https://www.ncbi.nlm.nih.gov/pubmed/21127054 http://dx.doi.org/10.1074/jbc.M110.200295 |
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author | Dominguez, Veronica Raimondi, Claudio Somanath, Sangeeta Bugliani, Marco Loder, Merewyn K. Edling, Charlotte E. Divecha, Nullin da Silva-Xavier, Gabriela Marselli, Lorella Persaud, Shanta J. Turner, Mark D. Rutter, Guy A. Marchetti, Piero Falasca, Marco Maffucci, Tania |
author_facet | Dominguez, Veronica Raimondi, Claudio Somanath, Sangeeta Bugliani, Marco Loder, Merewyn K. Edling, Charlotte E. Divecha, Nullin da Silva-Xavier, Gabriela Marselli, Lorella Persaud, Shanta J. Turner, Mark D. Rutter, Guy A. Marchetti, Piero Falasca, Marco Maffucci, Tania |
author_sort | Dominguez, Veronica |
collection | PubMed |
description | Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. Furthermore, of the different PI3Ks, the class II isoforms were detected in β cells, although their role is still not well understood. Here we show that down-regulation of the class II PI3K isoform PI3K-C2α specifically impairs insulin granule exocytosis in rat insulinoma cells without affecting insulin content, the number of insulin granules at the plasma membrane, or the expression levels of key proteins involved in insulin secretion. Proteolysis of synaptosomal-associated protein of 25 kDa, a process involved in insulin granule exocytosis, is impaired in cells lacking PI3K-C2α. Finally, our data suggest that the mRNA for PI3K-C2α may be down-regulated in islets of Langerhans from type 2 diabetic compared with non-diabetic individuals. Our results reveal a critical role for PI3K-C2α in β cells and suggest that down-regulation of PI3K-C2α may be a feature of type 2 diabetes. |
format | Text |
id | pubmed-3039383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30393832011-03-03 Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells Dominguez, Veronica Raimondi, Claudio Somanath, Sangeeta Bugliani, Marco Loder, Merewyn K. Edling, Charlotte E. Divecha, Nullin da Silva-Xavier, Gabriela Marselli, Lorella Persaud, Shanta J. Turner, Mark D. Rutter, Guy A. Marchetti, Piero Falasca, Marco Maffucci, Tania J Biol Chem Signal Transduction Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. Furthermore, of the different PI3Ks, the class II isoforms were detected in β cells, although their role is still not well understood. Here we show that down-regulation of the class II PI3K isoform PI3K-C2α specifically impairs insulin granule exocytosis in rat insulinoma cells without affecting insulin content, the number of insulin granules at the plasma membrane, or the expression levels of key proteins involved in insulin secretion. Proteolysis of synaptosomal-associated protein of 25 kDa, a process involved in insulin granule exocytosis, is impaired in cells lacking PI3K-C2α. Finally, our data suggest that the mRNA for PI3K-C2α may be down-regulated in islets of Langerhans from type 2 diabetic compared with non-diabetic individuals. Our results reveal a critical role for PI3K-C2α in β cells and suggest that down-regulation of PI3K-C2α may be a feature of type 2 diabetes. American Society for Biochemistry and Molecular Biology 2011-02-11 2010-12-02 /pmc/articles/PMC3039383/ /pubmed/21127054 http://dx.doi.org/10.1074/jbc.M110.200295 Text en © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Signal Transduction Dominguez, Veronica Raimondi, Claudio Somanath, Sangeeta Bugliani, Marco Loder, Merewyn K. Edling, Charlotte E. Divecha, Nullin da Silva-Xavier, Gabriela Marselli, Lorella Persaud, Shanta J. Turner, Mark D. Rutter, Guy A. Marchetti, Piero Falasca, Marco Maffucci, Tania Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells |
title | Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells |
title_full | Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells |
title_fullStr | Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells |
title_full_unstemmed | Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells |
title_short | Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic β Cells |
title_sort | class ii phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic β cells |
topic | Signal Transduction |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039383/ https://www.ncbi.nlm.nih.gov/pubmed/21127054 http://dx.doi.org/10.1074/jbc.M110.200295 |
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