Abstract
Disruption of the PPP1R3A gene encoding the glycogen targeting subunit (G(M)/R-GL) of protein phosphatase 1 (PP1) causes substantial lowering of the glycogen synthase activity and a 10-fold decrease in the glycogen levels in skeletal muscle. Homozygous G(M)(-/-) mice show increased weight gain after 3 months of age and become obese,. weighing similar to20% more than their wild-type (WT) littermates after 12 months of age. Glucose tolerance is impaired in 11-month-old G(M)(-/-) mice, and their skeletal muscle is insulin-resistant at greater than or equal to 12 months of age. The massive abdominal and other fat depositions observed at this age are likely to be a consequence of impaired blood glucose utilization in skeletal muscle. PP1-G(M) activity, assayed after specific immunoadsorption, was absent from G(M)(-/-) mice and stimulated in the hind limb muscles of WT mice by intravenous infusion of insulin. PP1-R5/PTG, another glycogen targeted form of PP1, was not significantly stimulated by insulin in the skeletal muscle of WT mice but showed compensatory stimulation by insulin in G(M)(-/-) mice. Our results suggest that dysfunction of PP1-G(M) may contribute to the pathophysiology of human type 2 diabetes.
Original language | English |
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Pages (from-to) | 596-604 |
Number of pages | 8 |
Journal | Diabetes |
Volume | 52 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2003 |
Keywords
- RABBIT SKELETAL-MUSCLE
- REGULATORY SUBUNIT
- 3'-UNTRANSLATED REGION
- GLUCOSE-INTOLERANCE
- CELLULAR-REGULATION
- CATALYTIC SUBUNIT
- 3T3-L1 ADIPOCYTES
- SYNTHASE KINASE-3
- PHOSPHORYLATION
- POLYMORPHISM