Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1: influence of the genetic background.
J Mol Endocrinol
; 40(2): 47-59, 2008 Feb.
Article
in En
| MEDLINE
| ID: mdl-18234908
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).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muscle, Skeletal
/
Protein Subunits
/
Protein Phosphatase 1
/
Glycogen
Limits:
Animals
Language:
En
Journal:
J Mol Endocrinol
Journal subject:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Year:
2008
Document type:
Article
Affiliation country:
United kingdom