GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells

Ryota Usui, Daisuke Yabe, Muhammad Fauzi, Hisanori Goto, Ainur Botagarova, Shinsuke Tokumoto, Hisato Tatsuoka, Yumiko Tahara, Shizuka Kobayashi, Toshiya Manabe, Yoshihiro Baba, Tomohiro Kurosaki, Pedro Luis Herrera, Masahito Ogura, Kazuaki Nagashima, Nobuya Inagaki

研究成果: ジャーナルへの寄稿記事

抄録

The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca2+ release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca2+ release via the IP3 receptor is linked to GIIS potentiation. Recently, stromal interaction molecule (STIM) 1 was identified as a key regulator of store-operated Ca2+ entry (SOCE), but little is known about its contribution in GPR40 signaling. We show that GPR40-mediated potentiation of GIIS is abolished by knockdown of IP3 receptor 1 (IP3R1), STIM1 or Ca2+-channel Orai1 in insulin-secreting MIN6 cells. STIM1 and Orai1 knockdown significantly impaired SOCE and the increase of intracellular Ca2+ by the GPR40 agonist, fasiglifam. Furthermore, β-cell-specific STIM1 knockout mice showed impaired fasiglifam-mediated GIIS potentiation not only in isolated islets but also in vivo. These results indicate that the IP3R1/STIM1/Orai1 pathway plays an important role in GPR40-mediated SOCE initiation and GIIS potentiation in pancreatic β-cells.

元の言語英語
記事番号15562
ジャーナルScientific reports
9
発行部数1
DOI
出版物ステータス出版済み - 12 1 2019

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Inositol 1,4,5-Trisphosphate Receptors
Insulin
Glucose
Endoplasmic Reticulum
Inositol 1,4,5-Trisphosphate
Insulin-Secreting Cells
Knockout Mice
Fatty Acids

All Science Journal Classification (ASJC) codes

  • General

これを引用

GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells. / Usui, Ryota; Yabe, Daisuke; Fauzi, Muhammad; Goto, Hisanori; Botagarova, Ainur; Tokumoto, Shinsuke; Tatsuoka, Hisato; Tahara, Yumiko; Kobayashi, Shizuka; Manabe, Toshiya; Baba, Yoshihiro; Kurosaki, Tomohiro; Herrera, Pedro Luis; Ogura, Masahito; Nagashima, Kazuaki; Inagaki, Nobuya.

:: Scientific reports, 巻 9, 番号 1, 15562, 01.12.2019.

研究成果: ジャーナルへの寄稿記事

Usui, R, Yabe, D, Fauzi, M, Goto, H, Botagarova, A, Tokumoto, S, Tatsuoka, H, Tahara, Y, Kobayashi, S, Manabe, T, Baba, Y, Kurosaki, T, Herrera, PL, Ogura, M, Nagashima, K & Inagaki, N 2019, 'GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells', Scientific reports, 巻. 9, 番号 1, 15562. https://doi.org/10.1038/s41598-019-52048-1
Usui, Ryota ; Yabe, Daisuke ; Fauzi, Muhammad ; Goto, Hisanori ; Botagarova, Ainur ; Tokumoto, Shinsuke ; Tatsuoka, Hisato ; Tahara, Yumiko ; Kobayashi, Shizuka ; Manabe, Toshiya ; Baba, Yoshihiro ; Kurosaki, Tomohiro ; Herrera, Pedro Luis ; Ogura, Masahito ; Nagashima, Kazuaki ; Inagaki, Nobuya. / GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells. :: Scientific reports. 2019 ; 巻 9, 番号 1.
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abstract = "The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca2+ release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca2+ release via the IP3 receptor is linked to GIIS potentiation. Recently, stromal interaction molecule (STIM) 1 was identified as a key regulator of store-operated Ca2+ entry (SOCE), but little is known about its contribution in GPR40 signaling. We show that GPR40-mediated potentiation of GIIS is abolished by knockdown of IP3 receptor 1 (IP3R1), STIM1 or Ca2+-channel Orai1 in insulin-secreting MIN6 cells. STIM1 and Orai1 knockdown significantly impaired SOCE and the increase of intracellular Ca2+ by the GPR40 agonist, fasiglifam. Furthermore, β-cell-specific STIM1 knockout mice showed impaired fasiglifam-mediated GIIS potentiation not only in isolated islets but also in vivo. These results indicate that the IP3R1/STIM1/Orai1 pathway plays an important role in GPR40-mediated SOCE initiation and GIIS potentiation in pancreatic β-cells.",
author = "Ryota Usui and Daisuke Yabe and Muhammad Fauzi and Hisanori Goto and Ainur Botagarova and Shinsuke Tokumoto and Hisato Tatsuoka and Yumiko Tahara and Shizuka Kobayashi and Toshiya Manabe and Yoshihiro Baba and Tomohiro Kurosaki and Herrera, {Pedro Luis} and Masahito Ogura and Kazuaki Nagashima and Nobuya Inagaki",
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AU - Usui, Ryota

AU - Yabe, Daisuke

AU - Fauzi, Muhammad

AU - Goto, Hisanori

AU - Botagarova, Ainur

AU - Tokumoto, Shinsuke

AU - Tatsuoka, Hisato

AU - Tahara, Yumiko

AU - Kobayashi, Shizuka

AU - Manabe, Toshiya

AU - Baba, Yoshihiro

AU - Kurosaki, Tomohiro

AU - Herrera, Pedro Luis

AU - Ogura, Masahito

AU - Nagashima, Kazuaki

AU - Inagaki, Nobuya

PY - 2019/12/1

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N2 - The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca2+ release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca2+ release via the IP3 receptor is linked to GIIS potentiation. Recently, stromal interaction molecule (STIM) 1 was identified as a key regulator of store-operated Ca2+ entry (SOCE), but little is known about its contribution in GPR40 signaling. We show that GPR40-mediated potentiation of GIIS is abolished by knockdown of IP3 receptor 1 (IP3R1), STIM1 or Ca2+-channel Orai1 in insulin-secreting MIN6 cells. STIM1 and Orai1 knockdown significantly impaired SOCE and the increase of intracellular Ca2+ by the GPR40 agonist, fasiglifam. Furthermore, β-cell-specific STIM1 knockout mice showed impaired fasiglifam-mediated GIIS potentiation not only in isolated islets but also in vivo. These results indicate that the IP3R1/STIM1/Orai1 pathway plays an important role in GPR40-mediated SOCE initiation and GIIS potentiation in pancreatic β-cells.

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