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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Research Article|
November 12 2010
Insulin/phosphoinositide 3-kinase pathway accelerates the glucose-induced first-phase insulin secretion through TrpV2 recruitment in pancreatic β-cells
Kyota Aoyagi;
Kyota Aoyagi
1Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
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Mica Ohara-Imaizumi;
Mica Ohara-Imaizumi
1Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
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Chiyono Nishiwaki;
Chiyono Nishiwaki
1Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
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Yoko Nakamichi;
Yoko Nakamichi
1Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
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Shinya Nagamatsu
Shinya Nagamatsu
1
1Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
1To whom correspondence should be addressed (email shinya@ks.kyorin-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
June 14 2010
Revision Received:
September 16 2010
Accepted:
September 20 2010
Accepted Manuscript online:
September 20 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 432 (2): 375–386.
Article history
Received:
June 14 2010
Revision Received:
September 16 2010
Accepted:
September 20 2010
Accepted Manuscript online:
September 20 2010
Citation
Kyota Aoyagi, Mica Ohara-Imaizumi, Chiyono Nishiwaki, Yoko Nakamichi, Shinya Nagamatsu; Insulin/phosphoinositide 3-kinase pathway accelerates the glucose-induced first-phase insulin secretion through TrpV2 recruitment in pancreatic β-cells. Biochem J 1 December 2010; 432 (2): 375–386. doi: https://doi.org/10.1042/BJ20100864
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