| Insulin/phosphoinositide 3-kinase pathway accelerates the glucose-induced first-phase insulin secretion through TrpV2 recruitment in pancreatic β-cells. | |
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MedLine Citation:
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PMID: 20854263 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Functional insulin receptor and its downstream effector PI3K (phosphoinositide 3-kinase) have been identified in pancreatic β-cells, but their involvement in the regulation of insulin secretion from β-cells remains unclear. In the present study, we investigated the physiological role of insulin and PI3K in glucose-induced biphasic insulin exocytosis in primary cultured β-cells and insulinoma Min6 cells using total internal reflection fluorescent microscopy. The pretreatment of β-cells with insulin induced the rapid increase in intracellular Ca2+ levels and accelerated the exocytotic response without affecting the second-phase insulin secretion. The inhibition of PI3K not only abolished the insulin-induced rapid development of the exocytotic response, but also potentiated the second-phase insulin secretion. The rapid development of Ca2+ and accelerated exocytotic response induced by insulin were accompanied by the translocation of the Ca2+-permeable channel TrpV2 (transient receptor potential V2) in a PI3K-dependent manner. Inhibition of TrpV2 by the selective blocker tranilast, or the expression of shRNA (short-hairpin RNA) against TrpV2 suppressed the effect of insulin in the first phase, but the second phase was not affected. Thus our results demonstrate that insulin treatment induced the acceleration of the exocytotic response during the glucose-induced first-phase response by the insertion of TrpV2 into the plasma membrane in a PI3K-dependent manner. |
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Authors:
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Kyota Aoyagi; Mica Ohara-Imaizumi; Chiyono Nishiwaki; Yoko Nakamichi; Shinya Nagamatsu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 432 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-15 Completed Date: 2010-12-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 375-86 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Calcium Channels / genetics* Cell Line DNA / chemistry, genetics DNA, Complementary / genetics Exocytosis Growth Hormone / secretion Homeostasis Humans Insulin / physiology*, secretion Insulin-Secreting Cells / enzymology, physiology*, secretion Male Mice Mice, Inbred C57BL Molecular Sequence Data Open Reading Frames Phosphatidylinositol 3-Kinases / metabolism TRPV Cation Channels / genetics* Transfection |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channels; 0/DNA, Complementary; 0/TRPV Cation Channels; 0/Trpv2 protein, mouse; 11061-68-0/Insulin; 9002-72-6/Growth Hormone; 9007-49-2/DNA; EC 2.7.1.-/Phosphatidylinositol 3-Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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