Glucose transport rate and glycogen synthase activity both limit skeletal muscle glycogen accumulation.
We varied rates of glucose transport and glycogen synthase I (GS-I) activity (%GS-I) in isolated rat epitrochlearis muscle to examine the role of each process in determining the rate of glycogen accumulation. %GS-I was maintained at or above the fasting basal range during 3 h of incubation with 36 mM glucose and 60 microU/ml insulin. Lithium (2 mM LiCl) added to insulin increased glucose transport rate and muscle glycogen content compared with insulin alone. The glycogen synthase kinase-3beta inhibitor GF-109203 x (GF; 10 microM) maintained %GS-I about twofold higher than insulin with or without lithium but did not increase glycogen accumulation. When %GS-I was lowered below the fasting range by prolonged incubation with 36 mM glucose and 2 mU/ml insulin, raising rates of glucose transport with bpV(phen) or of %GS-I with GF produced additive increases in glycogen concentration. Phosphorylase activity was unaffected by GF or bpV(phen). In muscles of fed animals, %GS-I was approximately 30% lower than in those of fasted rats, and insulin-stimulated glycogen accumulation did not occur unless %GS-I was raised with GF. We conclude that the rate of glucose transport is rate limiting for glycogen accumulation unless %GS-I is below the fasting range, in which case both glucose transport rate and GS activity can limit glycogen accumulation.
Fisher
Jonathan S
JS
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. fisherjs@slu.edu
Nolte
Lorraine A
LA
Kawanaka
Kentaro
K
Han
Dong-Ho
DH
Jones
Terry E
TE
Holloszy
John O
JO
D000818:Animals; D001692:Biological Transport; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D038341:Glycogen Synthase Kinases; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D008301:Maleimides; D006003:Glycogen; D008094:Lithium; D006006:Glycogen Synthase; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005947:Glucose; C070515:bisindolylmaleimide I