Epinephrine Control of Glycogen Metabolism in Glycogen-associated Protein Phosphatase PP1G/RGLKnockout Mice

Abstract

The glycogen-associated protein phosphatase (PP1G/ R(GL))may play a central role in the hormonal control of glycogen metabolism in the skeletal muscle. Here, we investigated the in vivo epinephrine effect of glycogen metabolism in the skeletal muscle of the wild-type and R(GL) knockout mice. The administration of epinephrine increased blood glucose levels from 200 +/- +/- 20 to 325 +/- 20 mg/dl in both wild-type and knockout mice. Epinephrine decreased the glycogen synthase -/+ G6P ratio from 0.24 +/- 0.04 to 0.10 +/- 0.02 in the wild-type, and from 0.17 +/- 0.02 to 0.06 +/- 0.01 in the knockout mice. Conversely, the glycogen phosphorylase activity ratio increased from 0.21 +/- 0.04 to 0.65 +/- 0.07 and from 0.30 +/- 0.04 to 0.81 +/- 0.06 in the epinephrine treated wild-type and knockout mice respectively. The glycogen content of the knockout mice was substantially lower (27 percent) than that of both wild-type mice; and epinephrine decreased glycogen content in the wild-type and knockout mice. Also, in Western blot analysis there was no compensation of the other glycogen targeting components PTG/R5 and R6 in the knockout mice compared with the wild-type. Therefore, R(GL) is not required for the epinephrine stimulation of glycogen metabolism, and rather another phosphatase and/or regulatory subunit appears to be involved.