Effect of AICAR Treatment on Glycogen Metabolism in Skeletal Muscle

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 3; pp. 567 - 573
• Main Authors: ASCHENBACH, William G, HIRSHMAN, Michael F, FUJII, Nobuharu, SAKAMOTO, Kei, HOWLETT, Kirsten F, GOODYEAR, Laurie J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-03-2002
• Subjects: Acetyl-CoA Carboxylase - metabolism; Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - therapeutic use; AMP-Activated Protein Kinases; Animals; Biological and medical sciences; Blood Glucose - metabolism; Diabetes; Diabetes research; Enzyme Activation - drug effects; Enzymes; Glucose; Glucose - metabolism; Glycogen - metabolism; Glycogen Phosphorylase - metabolism; Glycogen Synthase - metabolism; Glycogenolysis; Isoenzymes - metabolism; Kinases; Kinetics; Lactic Acid - blood; Male; Metabolism; Metabolites; Multienzyme Complexes - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Musculoskeletal system; Mutation; Phosphorylation; Physiological aspects; Protein-Serine-Threonine Kinases - metabolism; Proteins; Pyruvic Acid - metabolism; Rats; Rats, Sprague-Dawley; Ribonucleotides - therapeutic use; United States
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.3.567

Effect of AICAR Treatment on Glycogen Metabolism in Skeletal Muscle
William G. Aschenbach ,
Michael F. Hirshman ,
Nobuharu Fujii ,
Kei Sakamoto ,
Kirsten F. Howlett and
Laurie J. Goodyear
From the Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
Abstract
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
α2 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 α2 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.
Footnotes
Address correspondence and reprint requests to Laurie J. Goodyear, Research Division, Joslin Diabetes Center, Boston, MA 02215.
E-mail: laurie.goodyear{at}joslin.harvard.edu .
Received for publication 6 September 2001 and accepted in revised form 12 November 2001.
ACC, acetyl-CoA carboxylase; AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside; AMPK, AMP-activated protein kinase; EPI,
epitrochlearis; F-6-P, fructose-6-phosphate; FDB, flexor digitorum brevis; G-6-P, glucose-6-phosphate; ZMP, 5-aminoimidazole-4-carboxamide
ribonucleotide.
DIABETES