Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle.
This study was designed to determine whether chronic chemical activation of AMP-activated protein kinase (AMPK) would increase glucose transporter GLUT-4 and hexokinase in muscles similarly to periodic elevation of AMPK that accompanies endurance exercise training. The adenosine analog, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), has previously been shown to be taken up by cells and phosphorylated to form a compound (5-aminoimidazole-4-carboxamide ribonucleotide) that mimics the effect of AMP on AMPK. A single injection of AICAR resulted in a marked increase in AMPK in epitrochlearis and gastrocnemius/plantaris muscles 60 min later. When rats were injected with AICAR (1 mg/g body wt) for 5 days in succession and were killed 1 day after the last injection, GLUT-4 was increased by 100% in epitrochlearis muscle and by 60% in gastrocnemius muscle in response to AICAR. Hexokinase was also increased approximately 2. 5-fold in the gastrocnemius/plantaris. Gastrocnemius glycogen content was twofold higher in AICAR-treated rats than in controls. Chronic chemical activation of AMPK, therefore, results in increases in GLUT-4 protein, hexokinase activity, and glycogen, similarly to those induced by endurance training.
Holmes
B F
BF
Department of Zoology, Brigham Young University, Provo, Utah 84602, USA.
Kurth-Kraczek
E J
EJ
Winder
W W
WW
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology
D001786:Blood Glucose; D020536:Enzyme Activators; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012265:Ribonucleotides; C495694:Slc2a4 protein, rat; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; D006593:Hexokinase; D017868:Cyclic AMP-Dependent Protein Kinases; C031143:AICA ribonucleotide