Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca2+] elevation signals

Kazuhiro Eto; Tokuyuki Yamashita; Yoshiharu Tsubamoto; Yasuo Terauchi; Kenzo Hirose; Naoto Kubota; Shigeo Yamashita; Junko Taka; Shinobu Satoh; Hisahiko Sekihara; Kazuyuk Tobe; Masamitsu Iino; Mitsuhiko Noda; Satoshi Kimura; Takashi Kadowaki

doi:10.2337/diabetes.51.1.87

Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca²⁺] elevation signals

Kazuhiro Eto, Tokuyuki Yamashita, Yoshiharu Tsubamoto, Yasuo Terauchi, Kenzo Hirose, Naoto Kubota, Shigeo Yamashita, Junko Taka, Shinobu Satoh, Hisahiko Sekihara, Kazuyuk Tobe, Masamitsu Iino, Mitsuhiko Noda, Satoshi Kimura, Takashi Kadowaki^*

^*Corresponding author for this work

Internal Medicine （1）

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

The role of phosphatidylinositol (PI) 3-kinase in the regulation of pancreatic β-cell function was investigated. PI 3-kinase activity in p85α regulatory subunit-deficient (p85α^-/- islets was decreased to ∼20% of that in wild-type controls. Insulin content and mass of rough endoplasmic reticula were decreased in β-cells from p85α^-/- mice with increased insulin sensitivity. However, p85α^-/- β-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. When PI 3-kinase in wild-type islets was suppressed by wortmannin or LY294002, the secretion was also substantially potentiated. Wortmannin's potentiating effect was not due to augmentation in glucose metabolism or cytosolic [Ca²⁺] elevation. Results of p85α^-/- islets and wortmannin-treated wild-type islets stimulated with diazoxide and KC1 showed that inhibition of PI 3-kinase activity exerted its effect on secretion, at least in part, distal to a cytosolic [Ca²⁺] elevation. These results suggest that PI 3-kinase activity normally plays a crucial role in the suppression of glucose-stimulated insulin secretion.

Original language	English
Pages (from-to)	87-97
Number of pages	11
Journal	Diabetes
Volume	51
Issue number	1
DOIs	https://doi.org/10.2337/diabetes.51.1.87
State	Published - 2002

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.2337/diabetes.51.1.87

Cite this

Eto, K., Yamashita, T., Tsubamoto, Y., Terauchi, Y., Hirose, K., Kubota, N., Yamashita, S., Taka, J., Satoh, S., Sekihara, H., Tobe, K., Iino, M., Noda, M., Kimura, S., & Kadowaki, T. (2002). Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca²⁺] elevation signals. Diabetes, 51(1), 87-97. https://doi.org/10.2337/diabetes.51.1.87

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title = "Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca2+] elevation signals",

abstract = "The role of phosphatidylinositol (PI) 3-kinase in the regulation of pancreatic β-cell function was investigated. PI 3-kinase activity in p85α regulatory subunit-deficient (p85α-/- islets was decreased to ∼20% of that in wild-type controls. Insulin content and mass of rough endoplasmic reticula were decreased in β-cells from p85α-/- mice with increased insulin sensitivity. However, p85α-/- β-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. When PI 3-kinase in wild-type islets was suppressed by wortmannin or LY294002, the secretion was also substantially potentiated. Wortmannin's potentiating effect was not due to augmentation in glucose metabolism or cytosolic [Ca2+] elevation. Results of p85α-/- islets and wortmannin-treated wild-type islets stimulated with diazoxide and KC1 showed that inhibition of PI 3-kinase activity exerted its effect on secretion, at least in part, distal to a cytosolic [Ca2+] elevation. These results suggest that PI 3-kinase activity normally plays a crucial role in the suppression of glucose-stimulated insulin secretion.",

author = "Kazuhiro Eto and Tokuyuki Yamashita and Yoshiharu Tsubamoto and Yasuo Terauchi and Kenzo Hirose and Naoto Kubota and Shigeo Yamashita and Junko Taka and Shinobu Satoh and Hisahiko Sekihara and Kazuyuk Tobe and Masamitsu Iino and Mitsuhiko Noda and Satoshi Kimura and Takashi Kadowaki",

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doi = "10.2337/diabetes.51.1.87",

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Eto, K, Yamashita, T, Tsubamoto, Y, Terauchi, Y, Hirose, K, Kubota, N, Yamashita, S, Taka, J, Satoh, S, Sekihara, H, Tobe, K, Iino, M, Noda, M, Kimura, S & Kadowaki, T 2002, 'Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca²⁺] elevation signals', Diabetes, vol. 51, no. 1, pp. 87-97. https://doi.org/10.2337/diabetes.51.1.87

TY - JOUR

T1 - Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca2+] elevation signals

AU - Eto, Kazuhiro

AU - Yamashita, Tokuyuki

AU - Tsubamoto, Yoshiharu

AU - Terauchi, Yasuo

AU - Hirose, Kenzo

AU - Kubota, Naoto

AU - Yamashita, Shigeo

AU - Taka, Junko

AU - Satoh, Shinobu

AU - Sekihara, Hisahiko

AU - Tobe, Kazuyuk

AU - Iino, Masamitsu

AU - Noda, Mitsuhiko

AU - Kimura, Satoshi

AU - Kadowaki, Takashi

PY - 2002

Y1 - 2002

N2 - The role of phosphatidylinositol (PI) 3-kinase in the regulation of pancreatic β-cell function was investigated. PI 3-kinase activity in p85α regulatory subunit-deficient (p85α-/- islets was decreased to ∼20% of that in wild-type controls. Insulin content and mass of rough endoplasmic reticula were decreased in β-cells from p85α-/- mice with increased insulin sensitivity. However, p85α-/- β-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. When PI 3-kinase in wild-type islets was suppressed by wortmannin or LY294002, the secretion was also substantially potentiated. Wortmannin's potentiating effect was not due to augmentation in glucose metabolism or cytosolic [Ca2+] elevation. Results of p85α-/- islets and wortmannin-treated wild-type islets stimulated with diazoxide and KC1 showed that inhibition of PI 3-kinase activity exerted its effect on secretion, at least in part, distal to a cytosolic [Ca2+] elevation. These results suggest that PI 3-kinase activity normally plays a crucial role in the suppression of glucose-stimulated insulin secretion.

AB - The role of phosphatidylinositol (PI) 3-kinase in the regulation of pancreatic β-cell function was investigated. PI 3-kinase activity in p85α regulatory subunit-deficient (p85α-/- islets was decreased to ∼20% of that in wild-type controls. Insulin content and mass of rough endoplasmic reticula were decreased in β-cells from p85α-/- mice with increased insulin sensitivity. However, p85α-/- β-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. When PI 3-kinase in wild-type islets was suppressed by wortmannin or LY294002, the secretion was also substantially potentiated. Wortmannin's potentiating effect was not due to augmentation in glucose metabolism or cytosolic [Ca2+] elevation. Results of p85α-/- islets and wortmannin-treated wild-type islets stimulated with diazoxide and KC1 showed that inhibition of PI 3-kinase activity exerted its effect on secretion, at least in part, distal to a cytosolic [Ca2+] elevation. These results suggest that PI 3-kinase activity normally plays a crucial role in the suppression of glucose-stimulated insulin secretion.

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U2 - 10.2337/diabetes.51.1.87

DO - 10.2337/diabetes.51.1.87

M3 - 学術論文

C2 - 11756327

AN - SCOPUS:0036097594

SN - 0012-1797

VL - 51

SP - 87

EP - 97

JO - Diabetes

JF - Diabetes

IS - 1

ER -