Effect of AICAR treatment on glycogen metabolism in skeletal muscle.
AMP-activated protein kinase (AMPK) is proposed to stimulate fat and carbohydrate catabolism to maintain cellular energy status. Recent studies demonstrate that pharmacologic activation of AMPK and mutations in the enzyme are associated with elevated muscle glycogen content in vivo. Our purpose was to determine the mechanism for increased muscle glycogen associated with AMPK activity in vivo. AMPK activity and glycogen metabolism were studied in red and white gastrocnemius muscles from rats treated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in vivo, and also in muscles incubated with AICAR in vitro. In vivo AICAR treatment reduced blood glucose and increased blood lactate compared with basal values. AICAR increased muscle alpha2 AMPK activity, glycogen, and glucose-6-phosphate concentrations. Glycogen synthase activity was increased in the red gastrocnemius but was decreased in the white gastrocnemius. Glycogen phosphorylase activity increased in both muscles, with an inhibition initially observed in the red gastrocnemius. In vitro incubation with AICAR activated alpha2 AMPK but had no effect on either glycogen synthase or glycogen phosphorylase. These results suggest that AICAR treatment does not promote glycogen accumulation in skeletal muscle in vivo by altering glycogen synthase and glycogen phosphorylase. Rather, the increased glycogen is due to the well-known effects of AICAR to increase glucose uptake.
Aschenbach
William G
WG
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Hirshman
Michael F
MF
Fujii
Nobuharu
N
Sakamoto
Kei
K
Howlett
Kirsten F
KF
Goodyear
Laurie J
LJ
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000627:therapeutic use*
D001786:Blood Glucose; D007527:Isoenzymes; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D019344:Lactic Acid; D000620:Aminoimidazole Carboxamide; D019289:Pyruvic Acid; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D005947:Glucose