title: The muscle-specific protein phosphatase PP1G/R(GL)(G(M))is essential for activation of glycogen synthase by exercise.
abstract: In skeletal muscle both insulin and contractile activity are physiological stimuli for glycogen synthesis, which is thought to result in part from the dephosphorylation and activation of glycogen synthase (GS). PP1G/R(GL)(G(M)) is a glycogen/sarcoplasmic reticulum-associated type 1 phosphatase that was originally postulated to mediate insulin control of glycogen metabolism. However, we recently showed (Suzuki, Y., Lanner, C., Kim, J.-H., Vilardo, P. G., Zhang, H., Jie Yang, J., Cooper, L. D., Steele, M., Kennedy, A., Bock, C., Scrimgeour, A., Lawrence, J. C. Jr., L., and DePaoli-Roach, A. A. (2001) Mol. Cell. Biol. 21, 2683-2694) that insulin activates GS in muscle of R(GL)(G(M)) knockout (KO) mice similarly to the wild type (WT). To determine whether PP1G is involved in glycogen metabolism during muscle contractions, R(GL) KO and overexpressors (OE) were subjected to two models of contraction, in vivo treadmill running and in situ electrical stimulation. Both procedures resulted in a 2-fold increase in the GS -/+ glucose-6-P activity ratio in WT mice, but this response was completely absent in the KO mice. The KO mice, which also have a reduced GS activity associated with significantly reduced basal glycogen levels, exhibited impaired maximal exercise capacity, but contraction-induced activation of glucose transport was unaffected. The R(GL) OE mice are characterized by enhanced GS activity ratio and an approximately 3-4-fold increase in glycogen content in skeletal muscle. These animals were able to tolerate exercise normally. Stimulation of GS and glucose uptake following muscle contraction was not significantly different as compared with WT littermates. These results indicate that although PP1G/R(GL) is not necessary for activation of GS by insulin, it is essential for regulation of glycogen metabolism under basal conditions and in response to contractile activity, and may explain the reduced muscle glycogen content in the R(GL) KO mice, despite the normal insulin activation of GS.
authors.affiliation: Research Division, Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Aschenbach
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Breeden
authors.forename: C
authors.initials: C
authors.lastname: Prats
authors.forename: M F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: S D
authors.initials: SD
authors.lastname: Dufresne
authors.forename: K
authors.initials: K
authors.lastname: Sakamoto
authors.forename: P G
authors.initials: PG
authors.lastname: Vilardo
authors.forename: M
authors.initials: M
authors.lastname: Steele
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: S L
authors.initials: SL
authors.lastname: Jing
authors.forename: L J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: A A
authors.initials: AA
authors.lastname: DePaoli-Roach
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D004789:Enzyme Activation; D017079:Exercise Tolerance / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D054645:Protein Phosphatase 1
chemical_list: D002352:Carrier Proteins; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D010749:Phosphoprotein Phosphatases; C498442:Ppp1r3b protein, mouse; D054645:Protein Phosphatase 1; D005947:Glucose