Growth hormone inhibition of glucose uptake in adipocytes occurs without affecting GLUT4 translocation through an insulin receptor substrate-2-phosphatidylinositol 3-kinase-dependent pathway

Naoko Sasaki-Suzuki, Kiyoshi Arai, Tomomi Ogata, Kouhei Kasahara, Hideyuki Sakoda, Kazuhiro Chida, Tomoichiro Asano, Jeffrey E. Pessin, Fumihiko Hakuno, Shin Ichiro Takahashi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Growth hormone (GH) pretreatment of 3T3-L1 adipocytes resulted in a concentration- and time-dependent inhibition of insulin-stimulated glucose uptake. Surprisingly, this occurred without significant effect on insulin-stimulated glucose transporter (GLUT) 4 translocation or fusion with the plasma membrane. In parallel, the inhibitory actions of chronic GH pretreatment also impaired insulin-dependent activation of phosphatidylinositol (PI) 3-kinase bound to insulin receptor substrate (IRS)-2 but not to IRS-1. In addition, insulin-stimulated Akt phosphorylation was inhibited by GH pretreatment. In contrast, overexpression of IRS-2 or expression of a constitutively active Akt mutant prevented the GH-induced insulin resistance of glucose uptake. Moreover, small interfering RNA-mediated IRS-2 knockdown also inhibited insulin-stimulated Akt activation and glucose uptake without affecting GLUT4 translocation and plasma membrane fusion. Together, these data support a model in which chronic GH stimulation inhibits insulin-dependent activation of phosphatidylinositol 3-kinase through a specific interaction of phosphatidylinositol 3-kinase bound to IRS-2. This inhibition leads to suppression of Akt activation coupled to glucose transport activity bur not translocation or plasma membrane fusion of GLUT4.

Original languageEnglish (US)
Pages (from-to)6061-6070
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number10
DOIs
StatePublished - Mar 6 2009

Fingerprint

Phosphatidylinositol 3-Kinase
Insulin Receptor Substrate Proteins
Adipocytes
Growth Hormone
Insulin
Glucose
Cell membranes
Chemical activation
Membrane Fusion
Cell Membrane
Fusion reactions
Facilitative Glucose Transport Proteins
Phosphorylation
Small Interfering RNA
Insulin Resistance

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Growth hormone inhibition of glucose uptake in adipocytes occurs without affecting GLUT4 translocation through an insulin receptor substrate-2-phosphatidylinositol 3-kinase-dependent pathway. / Sasaki-Suzuki, Naoko; Arai, Kiyoshi; Ogata, Tomomi; Kasahara, Kouhei; Sakoda, Hideyuki; Chida, Kazuhiro; Asano, Tomoichiro; Pessin, Jeffrey E.; Hakuno, Fumihiko; Takahashi, Shin Ichiro.

In: Journal of Biological Chemistry, Vol. 284, No. 10, 06.03.2009, p. 6061-6070.

Research output: Contribution to journalArticle

Sasaki-Suzuki, Naoko ; Arai, Kiyoshi ; Ogata, Tomomi ; Kasahara, Kouhei ; Sakoda, Hideyuki ; Chida, Kazuhiro ; Asano, Tomoichiro ; Pessin, Jeffrey E. ; Hakuno, Fumihiko ; Takahashi, Shin Ichiro. / Growth hormone inhibition of glucose uptake in adipocytes occurs without affecting GLUT4 translocation through an insulin receptor substrate-2-phosphatidylinositol 3-kinase-dependent pathway. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 10. pp. 6061-6070.
@article{17db4e9c7efd451eaadf1ec874d9f9ab,
title = "Growth hormone inhibition of glucose uptake in adipocytes occurs without affecting GLUT4 translocation through an insulin receptor substrate-2-phosphatidylinositol 3-kinase-dependent pathway",
abstract = "Growth hormone (GH) pretreatment of 3T3-L1 adipocytes resulted in a concentration- and time-dependent inhibition of insulin-stimulated glucose uptake. Surprisingly, this occurred without significant effect on insulin-stimulated glucose transporter (GLUT) 4 translocation or fusion with the plasma membrane. In parallel, the inhibitory actions of chronic GH pretreatment also impaired insulin-dependent activation of phosphatidylinositol (PI) 3-kinase bound to insulin receptor substrate (IRS)-2 but not to IRS-1. In addition, insulin-stimulated Akt phosphorylation was inhibited by GH pretreatment. In contrast, overexpression of IRS-2 or expression of a constitutively active Akt mutant prevented the GH-induced insulin resistance of glucose uptake. Moreover, small interfering RNA-mediated IRS-2 knockdown also inhibited insulin-stimulated Akt activation and glucose uptake without affecting GLUT4 translocation and plasma membrane fusion. Together, these data support a model in which chronic GH stimulation inhibits insulin-dependent activation of phosphatidylinositol 3-kinase through a specific interaction of phosphatidylinositol 3-kinase bound to IRS-2. This inhibition leads to suppression of Akt activation coupled to glucose transport activity bur not translocation or plasma membrane fusion of GLUT4.",
author = "Naoko Sasaki-Suzuki and Kiyoshi Arai and Tomomi Ogata and Kouhei Kasahara and Hideyuki Sakoda and Kazuhiro Chida and Tomoichiro Asano and Pessin, {Jeffrey E.} and Fumihiko Hakuno and Takahashi, {Shin Ichiro}",
year = "2009",
month = "3",
day = "6",
doi = "10.1074/jbc.M808282200",
language = "English (US)",
volume = "284",
pages = "6061--6070",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

TY - JOUR

T1 - Growth hormone inhibition of glucose uptake in adipocytes occurs without affecting GLUT4 translocation through an insulin receptor substrate-2-phosphatidylinositol 3-kinase-dependent pathway

AU - Sasaki-Suzuki, Naoko

AU - Arai, Kiyoshi

AU - Ogata, Tomomi

AU - Kasahara, Kouhei

AU - Sakoda, Hideyuki

AU - Chida, Kazuhiro

AU - Asano, Tomoichiro

AU - Pessin, Jeffrey E.

AU - Hakuno, Fumihiko

AU - Takahashi, Shin Ichiro

PY - 2009/3/6

Y1 - 2009/3/6

N2 - Growth hormone (GH) pretreatment of 3T3-L1 adipocytes resulted in a concentration- and time-dependent inhibition of insulin-stimulated glucose uptake. Surprisingly, this occurred without significant effect on insulin-stimulated glucose transporter (GLUT) 4 translocation or fusion with the plasma membrane. In parallel, the inhibitory actions of chronic GH pretreatment also impaired insulin-dependent activation of phosphatidylinositol (PI) 3-kinase bound to insulin receptor substrate (IRS)-2 but not to IRS-1. In addition, insulin-stimulated Akt phosphorylation was inhibited by GH pretreatment. In contrast, overexpression of IRS-2 or expression of a constitutively active Akt mutant prevented the GH-induced insulin resistance of glucose uptake. Moreover, small interfering RNA-mediated IRS-2 knockdown also inhibited insulin-stimulated Akt activation and glucose uptake without affecting GLUT4 translocation and plasma membrane fusion. Together, these data support a model in which chronic GH stimulation inhibits insulin-dependent activation of phosphatidylinositol 3-kinase through a specific interaction of phosphatidylinositol 3-kinase bound to IRS-2. This inhibition leads to suppression of Akt activation coupled to glucose transport activity bur not translocation or plasma membrane fusion of GLUT4.

AB - Growth hormone (GH) pretreatment of 3T3-L1 adipocytes resulted in a concentration- and time-dependent inhibition of insulin-stimulated glucose uptake. Surprisingly, this occurred without significant effect on insulin-stimulated glucose transporter (GLUT) 4 translocation or fusion with the plasma membrane. In parallel, the inhibitory actions of chronic GH pretreatment also impaired insulin-dependent activation of phosphatidylinositol (PI) 3-kinase bound to insulin receptor substrate (IRS)-2 but not to IRS-1. In addition, insulin-stimulated Akt phosphorylation was inhibited by GH pretreatment. In contrast, overexpression of IRS-2 or expression of a constitutively active Akt mutant prevented the GH-induced insulin resistance of glucose uptake. Moreover, small interfering RNA-mediated IRS-2 knockdown also inhibited insulin-stimulated Akt activation and glucose uptake without affecting GLUT4 translocation and plasma membrane fusion. Together, these data support a model in which chronic GH stimulation inhibits insulin-dependent activation of phosphatidylinositol 3-kinase through a specific interaction of phosphatidylinositol 3-kinase bound to IRS-2. This inhibition leads to suppression of Akt activation coupled to glucose transport activity bur not translocation or plasma membrane fusion of GLUT4.

UR - http://www.scopus.com/inward/record.url?scp=65249086321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65249086321&partnerID=8YFLogxK

U2 - 10.1074/jbc.M808282200

DO - 10.1074/jbc.M808282200

M3 - Article

VL - 284

SP - 6061

EP - 6070

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 10

ER -