Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1

influence of the genetic background

James Paterson, Ian R. Kelsall, Patricia T. W. Cohen

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    A prediabetic phenotype of glucose intolerance, insulin resistance and obesity was observed at approximately 12 months of age in mice homozygous for a null allele of the major skeletal muscle glycogen-targeting subunit GM of protein phosphatase 1 (PP1) and derived from a 129/Ola donor strain. In this study, backcrossing of these GM-/- mice (termed obese GM-/- mice) onto two different genetic backgrounds gave rise to lean, glucose-tolerant, insulin-sensitive GM-/- mice (termed lean GM-/- mice), indicating that at least one variant gene in the 129/Ola background, not present in the C57BL/6 or 129s2/sV background, is required for the development of the prediabetic phenotype of obese mice. Slightly elevated AMP-activated protein kinase
    a2 activity in the skeletal muscle of lean C57BL/6 mice was also observed to a lesser extent in the obese GM-/- mice. Normal or slightly raised in vivo glucose transport in lean C57BL/6 GM-/- mice compared with decreased glucose transport in the obese GM-/- mice supports the tenet that adequate transport of glucose may be a key factor in preventing the development of the prediabetic phenotype. The pH 6.8/pH 8.6 activity ratio of phosphorylase kinase was increased in lean C57BL/6 GM-/- mice compared with controls indicating that phosphorylase kinase is an in vivo substrate of PP1-GM.

    Original languageEnglish
    Pages (from-to)47-59
    Number of pages13
    JournalJournal of Molecular Endocrinology
    Volume40
    Issue number2
    DOIs
    Publication statusPublished - Feb 2008

    Fingerprint

    Protein Phosphatase 1
    Striated Muscle
    Glycogen
    Obese Mice
    Phosphorylase Kinase
    Glucose
    Phenotype
    Skeletal Muscle
    AMP-Activated Protein Kinases
    Glucose Intolerance
    Inbreeding
    Inbred C57BL Mouse
    Insulin Resistance
    Genetic Background
    Obesity
    Alleles
    Insulin
    Genes

    Keywords

    • AMP-Activated Protein Kinases
    • Adipose Tissue
    • Animals
    • Crosses, Genetic
    • Environment
    • Female
    • Glucose
    • Glucose Tolerance Test
    • Glycogen
    • Hindlimb
    • Isoenzymes
    • Liver
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Multienzyme Complexes
    • Muscle, Skeletal
    • Phenotype
    • Protein Phosphatase 1
    • Protein Subunits
    • Protein-Serine-Threonine Kinases
    • Thinness

    Cite this

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    title = "Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1: influence of the genetic background",
    abstract = "A prediabetic phenotype of glucose intolerance, insulin resistance and obesity was observed at approximately 12 months of age in mice homozygous for a null allele of the major skeletal muscle glycogen-targeting subunit GM of protein phosphatase 1 (PP1) and derived from a 129/Ola donor strain. In this study, backcrossing of these GM-/- mice (termed obese GM-/- mice) onto two different genetic backgrounds gave rise to lean, glucose-tolerant, insulin-sensitive GM-/- mice (termed lean GM-/- mice), indicating that at least one variant gene in the 129/Ola background, not present in the C57BL/6 or 129s2/sV background, is required for the development of the prediabetic phenotype of obese mice. Slightly elevated AMP-activated protein kinase a2 activity in the skeletal muscle of lean C57BL/6 mice was also observed to a lesser extent in the obese GM-/- mice. Normal or slightly raised in vivo glucose transport in lean C57BL/6 GM-/- mice compared with decreased glucose transport in the obese GM-/- mice supports the tenet that adequate transport of glucose may be a key factor in preventing the development of the prediabetic phenotype. The pH 6.8/pH 8.6 activity ratio of phosphorylase kinase was increased in lean C57BL/6 GM-/- mice compared with controls indicating that phosphorylase kinase is an in vivo substrate of PP1-GM.",
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    author = "James Paterson and Kelsall, {Ian R.} and Cohen, {Patricia T. W.}",
    year = "2008",
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    doi = "10.1677/JME-07-0120",
    language = "English",
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    pages = "47--59",
    journal = "Journal of Molecular Endocrinology",
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    }

    Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1 : influence of the genetic background. / Paterson, James; Kelsall, Ian R.; Cohen, Patricia T. W.

    In: Journal of Molecular Endocrinology, Vol. 40, No. 2, 02.2008, p. 47-59.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1

    T2 - influence of the genetic background

    AU - Paterson, James

    AU - Kelsall, Ian R.

    AU - Cohen, Patricia T. W.

    PY - 2008/2

    Y1 - 2008/2

    N2 - A prediabetic phenotype of glucose intolerance, insulin resistance and obesity was observed at approximately 12 months of age in mice homozygous for a null allele of the major skeletal muscle glycogen-targeting subunit GM of protein phosphatase 1 (PP1) and derived from a 129/Ola donor strain. In this study, backcrossing of these GM-/- mice (termed obese GM-/- mice) onto two different genetic backgrounds gave rise to lean, glucose-tolerant, insulin-sensitive GM-/- mice (termed lean GM-/- mice), indicating that at least one variant gene in the 129/Ola background, not present in the C57BL/6 or 129s2/sV background, is required for the development of the prediabetic phenotype of obese mice. Slightly elevated AMP-activated protein kinase a2 activity in the skeletal muscle of lean C57BL/6 mice was also observed to a lesser extent in the obese GM-/- mice. Normal or slightly raised in vivo glucose transport in lean C57BL/6 GM-/- mice compared with decreased glucose transport in the obese GM-/- mice supports the tenet that adequate transport of glucose may be a key factor in preventing the development of the prediabetic phenotype. The pH 6.8/pH 8.6 activity ratio of phosphorylase kinase was increased in lean C57BL/6 GM-/- mice compared with controls indicating that phosphorylase kinase is an in vivo substrate of PP1-GM.

    AB - A prediabetic phenotype of glucose intolerance, insulin resistance and obesity was observed at approximately 12 months of age in mice homozygous for a null allele of the major skeletal muscle glycogen-targeting subunit GM of protein phosphatase 1 (PP1) and derived from a 129/Ola donor strain. In this study, backcrossing of these GM-/- mice (termed obese GM-/- mice) onto two different genetic backgrounds gave rise to lean, glucose-tolerant, insulin-sensitive GM-/- mice (termed lean GM-/- mice), indicating that at least one variant gene in the 129/Ola background, not present in the C57BL/6 or 129s2/sV background, is required for the development of the prediabetic phenotype of obese mice. Slightly elevated AMP-activated protein kinase a2 activity in the skeletal muscle of lean C57BL/6 mice was also observed to a lesser extent in the obese GM-/- mice. Normal or slightly raised in vivo glucose transport in lean C57BL/6 GM-/- mice compared with decreased glucose transport in the obese GM-/- mice supports the tenet that adequate transport of glucose may be a key factor in preventing the development of the prediabetic phenotype. The pH 6.8/pH 8.6 activity ratio of phosphorylase kinase was increased in lean C57BL/6 GM-/- mice compared with controls indicating that phosphorylase kinase is an in vivo substrate of PP1-GM.

    KW - AMP-Activated Protein Kinases

    KW - Adipose Tissue

    KW - Animals

    KW - Crosses, Genetic

    KW - Environment

    KW - Female

    KW - Glucose

    KW - Glucose Tolerance Test

    KW - Glycogen

    KW - Hindlimb

    KW - Isoenzymes

    KW - Liver

    KW - Male

    KW - Mice

    KW - Mice, Inbred C57BL

    KW - Multienzyme Complexes

    KW - Muscle, Skeletal

    KW - Phenotype

    KW - Protein Phosphatase 1

    KW - Protein Subunits

    KW - Protein-Serine-Threonine Kinases

    KW - Thinness

    U2 - 10.1677/JME-07-0120

    DO - 10.1677/JME-07-0120

    M3 - Article

    VL - 40

    SP - 47

    EP - 59

    JO - Journal of Molecular Endocrinology

    JF - Journal of Molecular Endocrinology

    SN - 0952-5041

    IS - 2

    ER -