Abstract
Aims/hypothesis. The glycogen-associated protein phosphatase-1 (PP1G) is thought to play an important part in the regulation of skeletal muscle glycogen content. We have previously identified an Asp905Tyr polymorphism of the glycogen-associated regulatory subunit of the protein phosphatase 1 (PPP1R3) gene which among healthy subjects was associated with decreased insulin stimulated non-oxidative glucose metabolism, i. e. primary glycogen synthesis. In this study, the functional effect of the polymorphism was examined in vitro.¶Methods. Wild type (PPP1R3-Asp905) and mutant (PPP1R3-Tyr905) PPP1R3 were expressed in L6 myotubes using adenovirus-mediated gene transfer. Basal and insulin-stimulated glucose uptake and glycogen synthesis were measured. Furthermore, the sensitivity of glycogen synthesis to a cyclic AMP agonist was measured.¶Results. Compared with green fluorescent protein-transduced myotubes and non-transduced myotubes, overexpression of PPP1R3-Asp905 and PPP1R3-Tyr905 increased both basal and insulin-stimulated glycogen synthesis approximately twofold. Treatment of both non-transduced and PPP1R3-transduced L6 myotubes with a cAMP agonist decreased both basal and insulin-stimulated glycogen synthesis by about 40 %. Overexpression of PPP1R3 did not affect either basal or insulin-stimulated 2-deoxy-d-glucose uptake compared with green fluorescent protein-transduced cells.¶Conclusion/interpretation. Results obtained from L6 myotubes transduced with PPP1R3-Asp905 or PPP1R3-Tyr905 showed no statistically significant difference. Therefore, the Asp905Tyr variant alone is unlikely to account for the decreased insulin stimulated non-oxidative glucose metabolism observed in the human study reported previously. [Diabetologia (2000) 43: 718–722]
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Received: 25 November 1999 and in revised form: 26 January 2000
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Rasmussen, S., Hansen, L., Frevert, E. et al. Adenovirus-mediated expression of a naturally occurring Asp905Tyr variant of the glycogen-associated regulatory subunit of protein phosphatase-1 in L6 myotubes. Diabetologia 43, 718–722 (2000). https://doi.org/10.1007/s001250051369
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DOI: https://doi.org/10.1007/s001250051369