Molecular Mechanism by Which AMP-Activated Protein Kinase Activation Promotes Glycogen Accumulation in Muscle

• DOI: 10.2337/db10-1148
• Publication Date: 2011-02-01T03:22:55Z
• Authors: Roger W. Hunter; Jonas T. Treebak; Jørgen F.P. Wojta...; Kei Sakamoto
• Keywords: AMP-Activated Protein Kinase; Glycogen debranching enzyme; Glycogen branching enzyme

During energy stress, AMP-activated protein kinase (AMPK) promotes glucose transport and glycolysis for ATP production, while it is thought to inhibit anabolic glycogen synthesis by suppressing the activity of synthase (GS) maintain balance in muscle. Paradoxically, chronic activation AMPK causes an increase accumulation skeletal cardiac muscles, which some cases associated with dysfunction. The aim this study was elucidate molecular mechanism muscle accumulation.We recently generated knock-in mice wild-type GS replaced a mutant (Arg582Ala) that could not be activated glucose-6-phosphate (G6P), but possessed full catalytic still normally dephosphorylation. Muscles from or transgenic overexpressing dead (KD) were incubated tracers AMPK-activating compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) ex vivo. uptake utilization (glycolysis synthesis) assessed.Even though AICAR caused modest inactivation GS, stimulated accompanied increases intracellular [G6P]. These effects required AMPK. Strikingly, AICAR-induced completely abolished G6P-insensitive mice, although AICAR-stimulated activation, transport, total normal.We provide genetic evidence allosteric through subsequent rise cellular