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

    7 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

    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

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