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Effect of AICAR treatment on gycogen metabolism in skeletal muscle
journal contribution
posted on 2002-03-01, 00:00 authored by W Aschenbach, M Hirschman, N Fujii, K Sakamoto, Kirsten HowlettKirsten Howlett, L GoodyearAMP-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.
History
Journal
DiabetesVolume
51Issue
3Pagination
567 - 573Publisher
American Diabetes AssociationLocation
New York, N.Y.ISSN
0012-1797eISSN
1939-327XLanguage
engPublication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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