Allosteric Regulation of Glycogen Synthase Controls Glycogen Synthesis in Muscle

• DOI: 10.1016/j.cmet.2010.10.006
• Publication Date: 2010-11-03T08:15:47Z
• Authors: Michale Bouskila; Roger W. Hunter; Adel F.M. Ibrahim; Lucie Delattre; Mark Peggie; Janna A. van Diepen; Peter J. Voshol; Jørgen Jensen; Kei Sakamoto
• Keywords: Glycogen debranching enzyme; Glycogen branching enzyme; GSK3B

SummaryGlycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and dephosphorylation through inactivation of GS kinase-3 with insulin. The relative importance these two regulatory mechanisms controlling not established, mainly due to complex interplay between multiple phosphorylation sites effectors. Here we identify residue that plays an important role activation G6P. We generated knockin mice which wild-type muscle was replaced mutant could be G6P but still normally dephosphorylation. demonstrate expressing G6P-insensitive display ∼80% reduced synthesis insulin markedly levels. Our study provides genetic evidence primary mechanism promotes accumulation vivo.Graphical abstractGraphical AbstractHighlights► A critical action site on (GS) identified ► mouse dramatically ability accumulate Insulin via