Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling

James W. A. Ritchie, Fiona E. Baird, Graham R. Christie, Alison Stewart, Sylvia Y. Low, Harinder S. Hundal, Peter M. Taylor

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    Adipose tissue is a major site for whole-body glutamine synthesis and we are investigating mechanisms and regulation of glutamine transport across the adipocyte membrane. Glutamine transport in adipocytes includes both high- and low-affinity Na+-dependent components (consistent with observed expression of ASCT2 and ATA2/SAT2 transporter mRNAs respectively) and a Na+-independent transport component (consistent with observed expression of LAT1/2 transporter mRNAs). Hypo-osmotic (235 mosmol/kg) swelling of adipocytes transiently stimulated glutamine uptake (180% increase at 0.05 mM glutamine) within 5 mins. Stimulation was blocked by the tyrosine kinase inhibitor genistein and the MAP kinase pathway inhibitors PD98059 and S13203580, but not by wortmannin (PI 3-kinase inhibitor) or rapamycin (mTOR pathway inhibitor). Cell-swelling also stimulated uptake of glucose but not MeAlB (indicating that ASCT2 rather than ATA2 was stimulated by swelling). Insulin (66 nM) treatment for up to 1 h stimulated Na+-dependent glutamine transport and increased adipocyte water space. Activation of the ERK1-2 MAP kinase pathway by cell swelling or insulin may be important for rapid activation of the ASCT2 glutamine transporter in adipocytes. Insulin may also exert a minor additional stimulatory effect on adipocyte glutamine transport indirectly via cell swelling. The mechanisms regulating glutamine transport in adipose tissue are distinct from those in other major sites of glutamine turnover in the body (notably liver and skeletal muscle). Copyright (C) 2001 S. Karger AG, Basel.
    Original languageEnglish
    Pages (from-to)259-270
    Number of pages12
    JournalCellular Physiology and Biochemistry
    Volume11
    Issue number5
    DOIs
    Publication statusPublished - 2001

    Cite this

    Ritchie, James W. A. ; Baird, Fiona E. ; Christie, Graham R. ; Stewart, Alison ; Low, Sylvia Y. ; Hundal, Harinder S. ; Taylor, Peter M. / Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling. In: Cellular Physiology and Biochemistry. 2001 ; Vol. 11, No. 5. pp. 259-270.
    @article{88ec48970d77411bbc2b5795ee8e57d1,
    title = "Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling",
    abstract = "Adipose tissue is a major site for whole-body glutamine synthesis and we are investigating mechanisms and regulation of glutamine transport across the adipocyte membrane. Glutamine transport in adipocytes includes both high- and low-affinity Na+-dependent components (consistent with observed expression of ASCT2 and ATA2/SAT2 transporter mRNAs respectively) and a Na+-independent transport component (consistent with observed expression of LAT1/2 transporter mRNAs). Hypo-osmotic (235 mosmol/kg) swelling of adipocytes transiently stimulated glutamine uptake (180{\%} increase at 0.05 mM glutamine) within 5 mins. Stimulation was blocked by the tyrosine kinase inhibitor genistein and the MAP kinase pathway inhibitors PD98059 and S13203580, but not by wortmannin (PI 3-kinase inhibitor) or rapamycin (mTOR pathway inhibitor). Cell-swelling also stimulated uptake of glucose but not MeAlB (indicating that ASCT2 rather than ATA2 was stimulated by swelling). Insulin (66 nM) treatment for up to 1 h stimulated Na+-dependent glutamine transport and increased adipocyte water space. Activation of the ERK1-2 MAP kinase pathway by cell swelling or insulin may be important for rapid activation of the ASCT2 glutamine transporter in adipocytes. Insulin may also exert a minor additional stimulatory effect on adipocyte glutamine transport indirectly via cell swelling. The mechanisms regulating glutamine transport in adipose tissue are distinct from those in other major sites of glutamine turnover in the body (notably liver and skeletal muscle). Copyright (C) 2001 S. Karger AG, Basel.",
    author = "Ritchie, {James W. A.} and Baird, {Fiona E.} and Christie, {Graham R.} and Alison Stewart and Low, {Sylvia Y.} and Hundal, {Harinder S.} and Taylor, {Peter M.}",
    year = "2001",
    doi = "10.1159/000047812",
    language = "English",
    volume = "11",
    pages = "259--270",
    journal = "Cellular Physiology and Biochemistry",
    issn = "1015-8987",
    publisher = "Karger",
    number = "5",

    }

    Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling. / Ritchie, James W. A. ; Baird, Fiona E.; Christie, Graham R. ; Stewart, Alison; Low, Sylvia Y. ; Hundal, Harinder S. ; Taylor, Peter M.

    In: Cellular Physiology and Biochemistry, Vol. 11, No. 5, 2001, p. 259-270.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling

    AU - Ritchie, James W. A.

    AU - Baird, Fiona E.

    AU - Christie, Graham R.

    AU - Stewart, Alison

    AU - Low, Sylvia Y.

    AU - Hundal, Harinder S.

    AU - Taylor, Peter M.

    PY - 2001

    Y1 - 2001

    N2 - Adipose tissue is a major site for whole-body glutamine synthesis and we are investigating mechanisms and regulation of glutamine transport across the adipocyte membrane. Glutamine transport in adipocytes includes both high- and low-affinity Na+-dependent components (consistent with observed expression of ASCT2 and ATA2/SAT2 transporter mRNAs respectively) and a Na+-independent transport component (consistent with observed expression of LAT1/2 transporter mRNAs). Hypo-osmotic (235 mosmol/kg) swelling of adipocytes transiently stimulated glutamine uptake (180% increase at 0.05 mM glutamine) within 5 mins. Stimulation was blocked by the tyrosine kinase inhibitor genistein and the MAP kinase pathway inhibitors PD98059 and S13203580, but not by wortmannin (PI 3-kinase inhibitor) or rapamycin (mTOR pathway inhibitor). Cell-swelling also stimulated uptake of glucose but not MeAlB (indicating that ASCT2 rather than ATA2 was stimulated by swelling). Insulin (66 nM) treatment for up to 1 h stimulated Na+-dependent glutamine transport and increased adipocyte water space. Activation of the ERK1-2 MAP kinase pathway by cell swelling or insulin may be important for rapid activation of the ASCT2 glutamine transporter in adipocytes. Insulin may also exert a minor additional stimulatory effect on adipocyte glutamine transport indirectly via cell swelling. The mechanisms regulating glutamine transport in adipose tissue are distinct from those in other major sites of glutamine turnover in the body (notably liver and skeletal muscle). Copyright (C) 2001 S. Karger AG, Basel.

    AB - Adipose tissue is a major site for whole-body glutamine synthesis and we are investigating mechanisms and regulation of glutamine transport across the adipocyte membrane. Glutamine transport in adipocytes includes both high- and low-affinity Na+-dependent components (consistent with observed expression of ASCT2 and ATA2/SAT2 transporter mRNAs respectively) and a Na+-independent transport component (consistent with observed expression of LAT1/2 transporter mRNAs). Hypo-osmotic (235 mosmol/kg) swelling of adipocytes transiently stimulated glutamine uptake (180% increase at 0.05 mM glutamine) within 5 mins. Stimulation was blocked by the tyrosine kinase inhibitor genistein and the MAP kinase pathway inhibitors PD98059 and S13203580, but not by wortmannin (PI 3-kinase inhibitor) or rapamycin (mTOR pathway inhibitor). Cell-swelling also stimulated uptake of glucose but not MeAlB (indicating that ASCT2 rather than ATA2 was stimulated by swelling). Insulin (66 nM) treatment for up to 1 h stimulated Na+-dependent glutamine transport and increased adipocyte water space. Activation of the ERK1-2 MAP kinase pathway by cell swelling or insulin may be important for rapid activation of the ASCT2 glutamine transporter in adipocytes. Insulin may also exert a minor additional stimulatory effect on adipocyte glutamine transport indirectly via cell swelling. The mechanisms regulating glutamine transport in adipose tissue are distinct from those in other major sites of glutamine turnover in the body (notably liver and skeletal muscle). Copyright (C) 2001 S. Karger AG, Basel.

    U2 - 10.1159/000047812

    DO - 10.1159/000047812

    M3 - Article

    VL - 11

    SP - 259

    EP - 270

    JO - Cellular Physiology and Biochemistry

    JF - Cellular Physiology and Biochemistry

    SN - 1015-8987

    IS - 5

    ER -