PMID:18234908
| Citation |
Paterson, J, Kelsall, IR and Cohen, PT (2008) Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1: influence of the genetic background. J. Mol. Endocrinol. 40:47-59 |
|---|---|
| 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 G(M) of protein phosphatase 1 (PP1) and derived from a 129/Ola donor strain. In this study, backcrossing of these G(M)-/- mice (termed obese G(M)-/- mice) onto two different genetic backgrounds gave rise to lean, glucose-tolerant, insulin-sensitive G(M)-/- mice (termed lean G(M)-/- 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 alpha2 activity in the skeletal muscle of lean C57BL/6 mice was also observed to a lesser extent in the obese G(M)-/- mice. Normal or slightly raised in vivo glucose transport in lean C57BL/6 G(M)-/- mice compared with decreased glucose transport in the obese G(M)-/- 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 G(M)-/- mice compared with controls indicating that phosphorylase kinase is an in vivo substrate of PP1-G(M). |
| Links |
PubMed Online version:10.1677/JME-07-0120 |
| Keywords |
AMP-Activated Protein Kinases; Adipose Tissue/metabolism; Animals; Crosses, Genetic; Environment; Female; Glucose/metabolism; Glucose Tolerance Test; Glycogen/metabolism; Hindlimb/enzymology; Isoenzymes/metabolism; Liver/metabolism; Male; Mice; Mice, Inbred C57BL; Multienzyme Complexes/metabolism; Muscle, Skeletal/enzymology; Phenotype; Protein Phosphatase 1/chemistry; Protein Phosphatase 1/genetics; Protein Phosphatase 1/metabolism; Protein Subunits/metabolism; Protein-Serine-Threonine Kinases/metabolism; Thinness |
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