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AICAR, the AMP kinase activator, inhibits glycogen formation and enhances lactate formation in L6 skeletal muscle cells
Author(s) -
Ouyang Jiangyong,
Ochs Raymond S.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a956-e
Subject(s) - glycogen , glycogen phosphorylase , glycogen synthase , glycogen branching enzyme , phosphorylase kinase , glycogen debranching enzyme , medicine , endocrinology , glycogenesis , chemistry , activator (genetics) , skeletal muscle , gsk 3 , biochemistry , protein kinase a , kinase , biology , gene
AICAR (5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside) is known to activate AMP kinase in muscle and to stimulate glucose uptake and fatty acid oxidation. We have confirmed these actions in the L6 skeletal muscle cell culture system. As it has also been established that AMP kinase can lead to an inactivation of glycogen synthase, we investigated the possibility that glycogen synthesis can be selectively inhibited in an intact muscle cell system. We showed that AICAR decreased glycogen synthesis in L6 cells, measured as labeled glucose incorporation into glycogen. When L6 cells were incubated with the glycogen phosphorylase inhibitor CP‐91149, AICAR remained an inhibitor of glycogen synthesis. Total glycogen content, however, was unaffected by AICAR. AICAR stimulated lactate production by L6 cells at low (0.5 mM) but not high (5 mM) glucose concentrations. We conclude that AICAR's actions may be extended to include an activation of glycogen breakdown (perhaps by AMP activation of glycogen phosphorylase), and an inactivation of glycogen synthase (perhaps by activation of AMP kinase). We also suggest that the pathway of glucose to lactate may or may not involve the intermediary formation of glycogen, depending on prevailing cellular conditions (such as energy status signaled by the AMP concentration), and the glucose concentration.